wikidoc - User contributions [en]

Splenic infarction overview

2016-09-26T04:51:31Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Splenic infarction}}
{{CMG}} {{AE}} {{asiri}}
==Overview==
A splenic [[infarct]] occurs when the vascular supply for the [[spleen]] becomes occluded leading to tissue [[hypoxia]] and [[necrosis]]. It can be the result of either [[arterial]] or [[venous]] compromise, and it is associated with multiple of disease states. The most common etiologies include [[malignancy]], [[thrombophilia|hypercoagulable disorders]], and [[embolism|embolic disorders]].<ref> Splenic infarction. Radiopedia.org (2015-2016). http://radiopaedia.org/articles/splenic-infarction Accessed on August 27, 2016</ref><ref name="pmid19328367">{{cite journal| author=Antopolsky M, Hiller N, Salameh S, Goldshtein B, Stalnikowicz R| title=Splenic infarction: 10 years of experience. | journal=Am J Emerg Med | year= 2009 | volume= 27 | issue= 3 | pages= 262-5 | pmid=19328367 | doi=10.1016/j.ajem.2008.02.014 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19328367 }} </ref> It is also common that splenic infarctions are the presenting signs of a previously unknown condition.<ref name="pmid20928991">{{cite journal| author=Lawrence YR, Pokroy R, Berlowitz D, Aharoni D, Hain D, Breuer GS| title=Splenic infarction: an update on William Osler's observations. | journal=Isr Med Assoc J | year= 2010 | volume= 12 | issue= 6 | pages= 362-5 | pmid=20928991 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20928991 }} </ref> Patients can be asymptomatic, however, most develop left upper quadrant [[abdominal pain]]. Splenic infarction is often diagnosed with [[computed tomography]]. Splenic infarcts can be managed medically, however, surgical intervention is indicated if the patient develops complications including [[hemorrhage]], rupture, [[abscess]], or [[pseudocyst]].<ref name="pmid3764696">{{cite journal |author=Jaroch MT, Broughan TA, Hermann RE |title=The natural history of splenic infarction |journal=Surgery |volume=100 |issue=4 |pages=743–50 |year=1986 |month=October |pmid=3764696 |doi= |url=}}</ref>

==Historical Perspective==

==Classification==

==Pathophysiology==

==Causes==

==Differentiating {{PAGENAME}} from Other Diseases==

==Epidemiology and Demographics==

==Risk Factors==

==Screening==

==Natural History, Complications, and Prognosis==
===Natural History===

===Complications===

===Prognosis===

==Diagnosis==
===Diagnostic Criteria===

===History and Symptoms===

===Physical Examination===

===Laboratory Findings===

===Imaging Findings===

===Other Diagnostic Studies===

==Treatment==
===Medical Therapy===

===Surgery===

===Prevention===

==References==
{{reflist|2}}
{{WH}}
{{WS}}

[[Category:Hematology]]

Splenic infarction overview

2016-08-28T17:47:15Z

Asiri Saumya Ediriwickrema: Update

__NOTOC__
{{Splenic infarction}}
{{CMG}} {{AE}} {{asiri}}
==Overview==
A splenic [[infarct]] occurs when the vascular supply for the [[spleen]] becomes occluded leading to tissue [[hypoxia]] and [[necrosis]]. It can be the result of either [[arterial]] or [[venous]] compromise, and it is associated with multiple of disease states. The most common etiologies include [[malignancy]], [[thrombophilia|hypercoagulable disorders]], and [[embolic disorders]].<ref> Splenic infarction. Radiopedia.org (2015-2016). http://radiopaedia.org/articles/splenic-infarction Accessed on August 27, 2016</ref><ref name="pmid19328367">{{cite journal| author=Antopolsky M, Hiller N, Salameh S, Goldshtein B, Stalnikowicz R| title=Splenic infarction: 10 years of experience. | journal=Am J Emerg Med | year= 2009 | volume= 27 | issue= 3 | pages= 262-5 | pmid=19328367 | doi=10.1016/j.ajem.2008.02.014 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19328367 }} </ref> It is also common that splenic infarctions are the presenting signs of a previously unknown condition.<ref name="pmid20928991">{{cite journal| author=Lawrence YR, Pokroy R, Berlowitz D, Aharoni D, Hain D, Breuer GS| title=Splenic infarction: an update on William Osler's observations. | journal=Isr Med Assoc J | year= 2010 | volume= 12 | issue= 6 | pages= 362-5 | pmid=20928991 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20928991 }} </ref> Patients can be asymptomatic, however, most develop left upper quadrant [[abdominal pain]]. Splenic infarction is often diagnosed with [[computed tomography]]. Splenic infarcts can be managed medically, however, surgical intervention is indicated if the patient develops complications including hemorrhage, rupture, abscess, or pseudocyst.<ref name="pmid3764696">{{cite journal |author=Jaroch MT, Broughan TA, Hermann RE |title=The natural history of splenic infarction |journal=Surgery |volume=100 |issue=4 |pages=743–50 |year=1986 |month=October |pmid=3764696 |doi= |url=}}</ref>

==Historical Perspective==

==Classification==

==Pathophysiology==

==Causes==

==Differentiating {{PAGENAME}} from Other Diseases==

==Epidemiology and Demographics==

==Risk Factors==

==Screening==

==Natural History, Complications, and Prognosis==
===Natural History===

===Complications===

===Prognosis===

==Diagnosis==
===Diagnostic Criteria===

===History and Symptoms===

===Physical Examination===

===Laboratory Findings===

===Imaging Findings===

===Other Diagnostic Studies===

==Treatment==
===Medical Therapy===

===Surgery===

===Prevention===

==References==
{{reflist|2}}
{{WH}}
{{WS}}

[[Category:Hematology]]

Splenic infarction

2016-08-27T18:29:12Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Infobox Disease
| Name = Splenic infarction
| Image = Splenic infarction.png
| Caption = Two large splenic infarcts, as demonstrated on an abdominal [[CT scan]] (white arrows) in a 36-year-old Caucasian woman with acute [[cytomegalovirus infection]]. The patient was also found to be heterozygous for the [[Factor V Leiden]] mutation.
| DiseasesDB = 12365
| ICD10 = {{ICD10|D|73|5|D|70}}
| ICD9 =
| ICDO =
| MedlinePlus = 001293
| MeshID = D013159
}}
{{Splenic infarction}}
{{CMG}} ; '''Associate Editor-In-Chief:''' {{asiri}} {{CZ}}

{{SK}} Spleen infarct, splenic artery thrombosis, splenic artery occlusion,

== [[Splenic infarction overview|Overview]] ==

== [[Splenic infarction historical perspective|Historical Perspective]]==

== [[Splenic infarction classification|Classification]] ==

== [[Splenic infarction pathophysiology|Pathophysiology]] ==

== [[Splenic infarction causes|Causes]] ==

== [[Splenic infarction differential diagnosis|Differentiating Splenic Infarction from other Diseases]] ==

== [[Splenic infarction epidemiology and demographics|Epidemiology and Demographics]]==

== [[Splenic infarction risk factors|Risk Factors]] ==

== [[Splenic infarction screening|Screening]] ==

== [[Splenic infarction natural history, complications and prognosis|Natural History, Complications and Prognosis]] ==

== Diagnosis ==
[[Splenic infarction history and symptoms|History and Symptoms]] | [[Splenic infarction physical examination|Physical Examination]] | [[Splenic infarction laboratory findings|Laboratory Findings]] | [[Splenic infarction electrocardiogram|Electrocardiogram]] | [[Splenic infarction chest x ray|Chest X Ray]] | [[Splenic infarction CT|CT]] | [[Splenic infarction MRI|MRI]] | [[Splenic infarction echocardiography or ultrasound|Ultrasound]] | [[Splenic infarction other imaging findings|Other Imaging Studies]] | [[Splenic infarction other diagnostic studies|Other Diagnostic Studies]]

== Treatment ==

[[Splenic infarction medical therapy|Medical Therapy]] | [[Splenic infarction surgery|Surgery]] | [[Splenic infarction primary prevention|Primary Prevention]] | [[Splenic infarction secondary prevention|Secondary Prevention]] | [[Splenic infarction cost-effectiveness of therapy | Cost Effectiveness of Therapy]] | [[Splenic infarction future or investigational therapies|Future or Investigational Therapies]]

==Case Studies==
:[[Splenic infarction case study one|Case #1]]

[[Category:Hematology]]

Splenic infarction

2016-08-27T03:15:43Z

Asiri Saumya Ediriwickrema: update

__NOTOC__
{{Infobox Disease
| Name = Splenic infarction
| Image = Splenic infarction.png
| Caption = Two large splenic infarcts, as demonstrated on an abdominal [[CT scan]] (white arrows) in a 36-year-old Caucasian woman with acute [[cytomegalovirus infection]]. The patient was also found to be heterozygous for the [[Factor V Leiden]] mutation.
| DiseasesDB = 12365
| ICD10 = {{ICD10|D|73|5|D|70}}
| ICD9 =
| ICDO =
| MedlinePlus = 001293
| MeshID = D013159
}}
{{Splenic infarction}}
{{CMG}} ; '''Associate Editor-In-Chief:''' {{CZ}} {{asiri}}

{{SK}} Spleen infarct, splenic artery thrombosis, splenic artery occlusion,

== [[Splenic infarction overview|Overview]] ==

== [[Splenic infarction historical perspective|Historical Perspective]]==

== [[Splenic infarction classification|Classification]] ==

== [[Splenic infarction pathophysiology|Pathophysiology]] ==

== [[Splenic infarction causes|Causes]] ==

== [[Splenic infarction differential diagnosis|Differentiating Splenic Infarction from other Diseases]] ==

== [[Splenic infarction epidemiology and demographics|Epidemiology and Demographics]]==

== [[Splenic infarction risk factors|Risk Factors]] ==

== [[Splenic infarction screening|Screening]] ==

== [[Splenic infarction natural history, complications and prognosis|Natural History, Complications and Prognosis]] ==

== Diagnosis ==
[[Splenic infarction history and symptoms|History and Symptoms]] | [[Splenic infarction physical examination|Physical Examination]] | [[Splenic infarction laboratory findings|Laboratory Findings]] | [[Splenic infarction electrocardiogram|Electrocardiogram]] | [[Splenic infarction chest x ray|Chest X Ray]] | [[Splenic infarction CT|CT]] | [[Splenic infarction MRI|MRI]] | [[Splenic infarction echocardiography or ultrasound|Ultrasound]] | [[Splenic infarction other imaging findings|Other Imaging Studies]] | [[Splenic infarction other diagnostic studies|Other Diagnostic Studies]]

== Treatment ==

[[Splenic infarction medical therapy|Medical Therapy]] | [[Splenic infarction surgery|Surgery]] | [[Splenic infarction primary prevention|Primary Prevention]] | [[Splenic infarction secondary prevention|Secondary Prevention]] | [[Splenic infarction cost-effectiveness of therapy | Cost Effectiveness of Therapy]] | [[Splenic infarction future or investigational therapies|Future or Investigational Therapies]]

==Case Studies==
:[[Splenic infarction case study one|Case #1]]

[[Category:Hematology]]

Thrombophilia medical therapy

2016-08-25T03:30:40Z

Asiri Saumya Ediriwickrema:

__NOTOC__

{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}
==Overview==
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

==Medical Therapy==
*The 2016 guidelines from the [https://www.chestnet.org American College of Chest Physicians (ACCP)] recommend that patients with provoked venous thrombosis from reversible risk factors should receive 3-6 months of anticoagulation<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
***Response to anticoagulation can be monitored clinically, with repeat ultrasongraphy for [[Deep_vein_thrombosis|deep vein thrombosis]] or measuring [[D-dimer]] levels after treatment
*The 2016 guidelines from the ACCP recommend that direct oral anticoagulants (DOACs), including [[Direct_Xa_inhibitor|direct Xa inhibitors]] and [[Direct_thrombin_inhibitor|direct thrombin inhibitors]], be used for long term treatment of most patients<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
:*Important exceptions include:
:**Pregnancy<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
:**Renal insufficiency
:**Malignancy<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
*[[Low_molecular_weight_heparin|Low molecular weight heparin (LMWH)]] is recommended for anticoagulation for the following acquired thrombophilias:
**'''Post-surgery prophylaxis'''<ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
***The duration of anticoagulation after surgery is variable. Most clinical trials have evaluated anticoagulation for 10-35 days
***General recommendations for thrombophrophylaxis is 7-10 days for standard risk patients and 10-35 days for higher risk patients as described in the algorithims below and for patients undergoing abdominal and pelvic surgeries for gynecologic malginancies<ref name="pmid20409525">{{cite journal| author=Muntz J| title=Duration of deep vein thrombosis prophylaxis in the surgical patient and its relation to quality issues. | journal=Am J Surg | year= 2010 | volume= 200 | issue= 3 | pages= 413-21 | pmid=20409525 | doi=10.1016/j.amjsurg.2009.05.045 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20409525 }} </ref>
***DOACs may be considered as agents for extended thromboprophylaxis after [[Deep_vein_thrombosis_landmark_trials_in_prevention|total hip replacement and total knee replacement]].
**'''Pregnancy and postpartum'''<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
***Patients who develop acute thrombosis during pregnancy should be anticoagulated for the remainder of the their pregnancy and 6 weeks postpartum for a minimum of 3 months
***A similar duration of anticoagulation is recommended for patients with high risk thrombophilias as described in the algorithims below
**'''Malignancy'''<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
*Alternative agents include [[Warfarin]] and [[Fondaparinux]]
**Warfarin is the agent of choice for prophylactic anticoagulation in patients with [[nephrotic syndrome]], as there are no studies evaluating DOACs and LMWH for this clinical indication. Refer to the treatment algorithim below. It is important to note that the recommendations for prophylactic anticoagulation in patients with nephrotic syndrome are not based on expert consensus guidelines.<ref name="pmid17599972">{{cite journal| author=Glassock RJ| title=Prophylactic anticoagulation in nephrotic syndrome: a clinical conundrum. | journal=J Am Soc Nephrol | year= 2007 | volume= 18 | issue= 8 | pages= 2221-5 | pmid=17599972 | doi=10.1681/ASN.2006111300 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17599972 }} </ref><ref name="pmid24336031">{{cite journal| author=Lee T, Biddle AK, Lionaki S, Derebail VK, Barbour SJ, Tannous S et al.| title=Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy. | journal=Kidney Int | year= 2014 | volume= 85 | issue= 6 | pages= 1412-20 | pmid=24336031 | doi=10.1038/ki.2013.476 | pmc=4040154 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24336031 }} </ref>
***Lee et al created an [https://www.unckidneycenter.org/gntools/index.html online tool] to assist in evaluating the benefits and risks of prophylactic anticoagulation in patients with [[membranous nephropathy]].

'''Treatment algorithims for both acquired and inherited thrombophilias are presented below:'''
*Thromboprophylaxis or indefinate anticoagulation may be required for certain inherited thrombophilias

[[Image: Thrombophilia_Management_Thrombosis.jpg|thumb|center|600px|Management of acute thrombosis in patients with inherited thrombophilias]]

[[Image: Thrombophilia_Inherited_Management.jpg|thumb|center|500px|Management of asymptomatic patients with inherited thrombophilias]]

[[Image: Thrombophilia_Acquired_Management.jpg|thumb|center|300px|Management of patients with acquired thrombophilias]]

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]

File:Thrombophilia Acquired Management.jpg

2016-08-17T23:17:20Z

Asiri Saumya Ediriwickrema: Asiri Saumya Ediriwickrema uploaded a new version of File:Thrombophilia Acquired Management.jpg

Thrombophilia medical therapy

2016-08-17T23:15:44Z

Asiri Saumya Ediriwickrema: update

__NOTOC__

{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}
==Overview==
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

==Medical Therapy==
*The 2016 guidelines from the [https://www.chestnet.org American College of Chest Physicians (ACCP)] recommend that patients with provoked venous thrombosis from reversible risk factors should receive 3-6 months of anticoagulation<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
***Response to anticoagulation can be monitored clinically, with repeat ultrasongraphy for [[Deep_vein_thrombosis|deep vein thrombosis]] or measuring [[D-dimer]] levels after treatment
*The 2016 guidelines from the ACCP recommend that direct oral anticoagulants (DOACs), including [[Direct_Xa_inhibitor|direct Xa inhibitors]] and [[Direct_thrombin_inhibitor|direct thrombin inhibitors]], be used for long term treatment of most patients<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
:*Important exceptions include:
:**Pregnancy<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
:**Renal insufficiency
:**Malignancy<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
*[[Low_molecular_weight_heparin|Low molecular weight heparin (LMWH)]] is recommended for anticoagulation for the following acquired thrombophilias:
**'''Post-surgery prophylaxis'''<ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
***The duration of anticoagulation after surgery is variable. Most clinical trials have evaluated anticoagulation for 10-35 days
***General recommendations for thrombophrophylaxis is 7-10 days for standard risk patients and 10-35 days for higher risk patients as described in the algorithims below and for patients undergoing abdominal and pelvic surgeries for gynecologic malginancies<ref name="pmid20409525">{{cite journal| author=Muntz J| title=Duration of deep vein thrombosis prophylaxis in the surgical patient and its relation to quality issues. | journal=Am J Surg | year= 2010 | volume= 200 | issue= 3 | pages= 413-21 | pmid=20409525 | doi=10.1016/j.amjsurg.2009.05.045 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20409525 }} </ref>
***DOACs may be considered as agents for extended thromboprophylaxis after [[Deep_vein_thrombosis_landmark_trials_in_prevention|total hip replacement and total knee replacement]].
**'''Pregnancy and postpartum'''<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
***Patients who develop acute thrombosis during pregnancy should be anticoagulated for the remainder of the their pregnancy and 6 weeks postpartum for a minimum of 3 months
***A similar duration of anticoagulation is recommended for patients with high risk thrombophilias as described in the algorithims below
**'''Malignancy'''<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
*Alternative agents include [[Warfarin]] and [[Fondaparinux]]
**Warfarin is the agent of choice for prophylactic anticoagulation in patients with [[nephrotic syndrome]], as there are no studies evaluating DOACs and LMWH for this clinical indication. Refer to the treatment algorithim below. It is important to note that the recommendations for prophylactic anticoagulation in patients with nephrotic syndrome are not based on expert consensus guidelines.<ref name="pmid17599972">{{cite journal| author=Glassock RJ| title=Prophylactic anticoagulation in nephrotic syndrome: a clinical conundrum. | journal=J Am Soc Nephrol | year= 2007 | volume= 18 | issue= 8 | pages= 2221-5 | pmid=17599972 | doi=10.1681/ASN.2006111300 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17599972 }} </ref><ref name="pmid24336031">{{cite journal| author=Lee T, Biddle AK, Lionaki S, Derebail VK, Barbour SJ, Tannous S et al.| title=Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy. | journal=Kidney Int | year= 2014 | volume= 85 | issue= 6 | pages= 1412-20 | pmid=24336031 | doi=10.1038/ki.2013.476 | pmc=4040154 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24336031 }} </ref>
***Lee et al created an [https://www.unckidneycenter.org/gntools/index.html online tool] to assist in evaluating the benefits and risks of prophylactic anticoagulation in patients with [[membranous nephropathy]].

'''Treatment algorithims for both acquired and inherited thrombophilias are presented below:'''
*Thromboprophylaxis or indefinate anticoagulation may be required for certain inherited thrombophilias

[[Image: Thrombophilia_Management_Thrombosis.jpg|thumb|center|600px|Management of acute thrombosis in patients with inherited thrombophilias]]

[[Image: Thrombophilia_Inherited_Management.jpg|thumb|center|500px|Management of asymptomatic patients with inherited thrombophilias]]

[[Image: Thrombophilia_Acquired_Management.jpg|thumb|center|500px|Management of patients with acquired thrombophilias]]

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]

Thrombophilia natural history, complications and prognosis

2016-07-21T19:44:58Z

Asiri Saumya Ediriwickrema: /* Prognosis */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref>

==Natural History==
* Refer to the [[Thrombophilia_history_and_symptoms|clinical symptoms]] section regarding early clinical features of patients with thrombophilia.
* If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) (<0.06%) is low.<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref>
* Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref>
* Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref>
* OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>
* Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

==Complications==
* The primary complication of thrombophilia is the development of [[Thrombus|blood clots]]
* Patients with primary hypercoagulable states develop thrombosis mostly in the settting of aquired risk factors which include [[trauma]], [[surgery]], [[immobility]], pregnancy and use of OCPs.
* [[Deep vein thrombosis]] and [[pulmonary embolus]] are the most common complications.

'''The risk of future thrombosis in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" |Thrombophilic state
! style="font-weight: bold;" |Thrombotic risk<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref>
|-
| Trauma/General surgery
| Modest
|-
| Age > 60
| Modest
|-
| Immobilization
| Modest
|-
| Pregnancy
| Modest
|-
| Hormone therapies
| Modest
|-
| Factor V Leiden heterozygosity
| Modest
|-
| Prothrombin mutation
| Modest
|-
| Homocysteinemia
| Modest
|-
| Increased factor VIII levels
| Modest
|-
| Increased factor IX levels
| Modest
|-
| Increased factor XI levels
| Modest
|-
| Protein C and S deficiency
| Intermediate
|-
| Dysfibrogenemia
| Intermediate
|-
| Malignancy
| High
|-
| APLS/Lupus anticoagulant
| High
|-
| Myeloproliferative disorders/hyperviscosity
| High
|-
| PNH
| High
|-
| Orthopedic surgery
| High
|-
| Antithrombin deficiency
| High
|-
| Factor V Leiden homozygosity
| High
|-
|}

'''The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" | Thrombophilic state
! style="font-weight: bold;" | Annual Incidence (%)
! style="font-weight: bold;" | Relative Risk
|-
| Normal
| 0.008
| 1
|-
| Factor V leiden heterozygous
| 0.06
| 3-10
|-
| Factor V leiden homozygous
| 0.5-1
| 80
|-
| Prothrombin G20210A
| 0.02
| 1-5
|-
| Oral contraceptive (OCP)
| 0.03
| 4
|-
| style="font-style: italic;" | OCP and factor V leiden heterozygous
| style="font-style: italic;" | 0.3
| style="font-style: italic;" | 35
|-
| style="font-style: italic;" | OCP and factor V leiden homozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 100
|-
| style="font-style: italic;" | OCP and prothrombin G20210A
| style="font-style: italic;" |
| style="font-style: italic;" | 16
|-
| style="font-style: italic;" | OCP and protein C/S, or antithrombin III deficiency
| style="font-style: italic;" |
| style="font-style: italic;" | 9.7
|-
| Pregnancy
|
| 7
|-
| style="font-style: italic;" | Pregnancy and factor V leiden heterozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 35
|-
| Cancer
|
| 5
|-
| History of venous thrombosis
|
| 50
|}
Data were extracted from multiple sources.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref><ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref><ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>

==Prognosis==
The prognosis depends on the underlying thrombophilia as each form has a different associated thrombotic risk. Patients who develop multiple or atyplical clots, arterial thrombosis, or life-threatening thrombosis have worse prognosis.

Thrombophilias generally associated with worse prognosis include:
*[[Antiphospholipid Syndrome]]
*[[Paroxysmal nocturnal hemoglobinuria]]
*[[Antithrombin III deficiency]]
*[[Factor V Leiden]] homozygosity

Certain thrombophilic conditions are high risk and require consideration for lifelong [[anticoagulation]]. In these cases, expert consultation is recommended.

{| class="wikitable"
! style="font-weight: bold;" | Possible indications for lifelong/prophylactic anticoagulation
|-
| Antiphospholipid syndrome
|-
| Paroxysmal nocturnal hemoglobinuria
|-
| Recurrent thrombosis regardless of underlying thrombophilia
|-
| History of life-threatening thrombosis or atypical locations
|-
| Malignancy with history of thrombosis
|}

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia natural history, complications and prognosis

2016-07-21T19:43:42Z

Asiri Saumya Ediriwickrema: /* Prognosis */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref>

==Natural History==
* Refer to the [[Thrombophilia_history_and_symptoms|clinical symptoms]] section regarding early clinical features of patients with thrombophilia.
* If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) (<0.06%) is low.<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref>
* Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref>
* Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref>
* OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>
* Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

==Complications==
* The primary complication of thrombophilia is the development of [[Thrombus|blood clots]]
* Patients with primary hypercoagulable states develop thrombosis mostly in the settting of aquired risk factors which include [[trauma]], [[surgery]], [[immobility]], pregnancy and use of OCPs.
* [[Deep vein thrombosis]] and [[pulmonary embolus]] are the most common complications.

'''The risk of future thrombosis in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" |Thrombophilic state
! style="font-weight: bold;" |Thrombotic risk<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref>
|-
| Trauma/General surgery
| Modest
|-
| Age > 60
| Modest
|-
| Immobilization
| Modest
|-
| Pregnancy
| Modest
|-
| Hormone therapies
| Modest
|-
| Factor V Leiden heterozygosity
| Modest
|-
| Prothrombin mutation
| Modest
|-
| Homocysteinemia
| Modest
|-
| Increased factor VIII levels
| Modest
|-
| Increased factor IX levels
| Modest
|-
| Increased factor XI levels
| Modest
|-
| Protein C and S deficiency
| Intermediate
|-
| Dysfibrogenemia
| Intermediate
|-
| Malignancy
| High
|-
| APLS/Lupus anticoagulant
| High
|-
| Myeloproliferative disorders/hyperviscosity
| High
|-
| PNH
| High
|-
| Orthopedic surgery
| High
|-
| Antithrombin deficiency
| High
|-
| Factor V Leiden homozygosity
| High
|-
|}

'''The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" | Thrombophilic state
! style="font-weight: bold;" | Annual Incidence (%)
! style="font-weight: bold;" | Relative Risk
|-
| Normal
| 0.008
| 1
|-
| Factor V leiden heterozygous
| 0.06
| 3-10
|-
| Factor V leiden homozygous
| 0.5-1
| 80
|-
| Prothrombin G20210A
| 0.02
| 1-5
|-
| Oral contraceptive (OCP)
| 0.03
| 4
|-
| style="font-style: italic;" | OCP and factor V leiden heterozygous
| style="font-style: italic;" | 0.3
| style="font-style: italic;" | 35
|-
| style="font-style: italic;" | OCP and factor V leiden homozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 100
|-
| style="font-style: italic;" | OCP and prothrombin G20210A
| style="font-style: italic;" |
| style="font-style: italic;" | 16
|-
| style="font-style: italic;" | OCP and protein C/S, or antithrombin III deficiency
| style="font-style: italic;" |
| style="font-style: italic;" | 9.7
|-
| Pregnancy
|
| 7
|-
| style="font-style: italic;" | Pregnancy and factor V leiden heterozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 35
|-
| Cancer
|
| 5
|-
| History of venous thrombosis
|
| 50
|}
Data were extracted from multiple sources.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref><ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref><ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>

==Prognosis==
The prognosis depends on the underlying thrombophilia as each form has a different associated thrombotic risk. Patients who develop multiple or atyplical clots, arterial thrombosis, or life-threatening thrombosis have worse prognosis.

Thrombophilias generally associated with worse prognosis include:
*[[Antiphospholipid Syndrome]]
*[[Paroxysmal nocturnal hemoglobinuria]]
*Antithrombin III deficiency
*[[Factor V Leiden]] homozygosity

Certain thrombophilic conditions are high risk and require consideration for lifelong [[anticoagulation]]. In these cases, expert consultation is recommended.

{| class="wikitable"
! style="font-weight: bold;" | Possible indications for lifelong/prophylactic anticoagulation
|-
| Antiphospholipid syndrome
|-
| Paroxysmal nocturnal hemoglobinuria
|-
| Recurrent thrombosis regardless of underlying thrombophilia
|-
| History of life-threatening thrombosis or atypical locations
|-
| Malignancy with history of thrombosis
|}

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia natural history, complications and prognosis

2016-07-21T19:43:02Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref>

==Natural History==
* Refer to the [[Thrombophilia_history_and_symptoms|clinical symptoms]] section regarding early clinical features of patients with thrombophilia.
* If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) (<0.06%) is low.<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref>
* Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref>
* Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref>
* OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>
* Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

==Complications==
* The primary complication of thrombophilia is the development of [[Thrombus|blood clots]]
* Patients with primary hypercoagulable states develop thrombosis mostly in the settting of aquired risk factors which include [[trauma]], [[surgery]], [[immobility]], pregnancy and use of OCPs.
* [[Deep vein thrombosis]] and [[pulmonary embolus]] are the most common complications.

'''The risk of future thrombosis in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" |Thrombophilic state
! style="font-weight: bold;" |Thrombotic risk<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref>
|-
| Trauma/General surgery
| Modest
|-
| Age > 60
| Modest
|-
| Immobilization
| Modest
|-
| Pregnancy
| Modest
|-
| Hormone therapies
| Modest
|-
| Factor V Leiden heterozygosity
| Modest
|-
| Prothrombin mutation
| Modest
|-
| Homocysteinemia
| Modest
|-
| Increased factor VIII levels
| Modest
|-
| Increased factor IX levels
| Modest
|-
| Increased factor XI levels
| Modest
|-
| Protein C and S deficiency
| Intermediate
|-
| Dysfibrogenemia
| Intermediate
|-
| Malignancy
| High
|-
| APLS/Lupus anticoagulant
| High
|-
| Myeloproliferative disorders/hyperviscosity
| High
|-
| PNH
| High
|-
| Orthopedic surgery
| High
|-
| Antithrombin deficiency
| High
|-
| Factor V Leiden homozygosity
| High
|-
|}

'''The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" | Thrombophilic state
! style="font-weight: bold;" | Annual Incidence (%)
! style="font-weight: bold;" | Relative Risk
|-
| Normal
| 0.008
| 1
|-
| Factor V leiden heterozygous
| 0.06
| 3-10
|-
| Factor V leiden homozygous
| 0.5-1
| 80
|-
| Prothrombin G20210A
| 0.02
| 1-5
|-
| Oral contraceptive (OCP)
| 0.03
| 4
|-
| style="font-style: italic;" | OCP and factor V leiden heterozygous
| style="font-style: italic;" | 0.3
| style="font-style: italic;" | 35
|-
| style="font-style: italic;" | OCP and factor V leiden homozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 100
|-
| style="font-style: italic;" | OCP and prothrombin G20210A
| style="font-style: italic;" |
| style="font-style: italic;" | 16
|-
| style="font-style: italic;" | OCP and protein C/S, or antithrombin III deficiency
| style="font-style: italic;" |
| style="font-style: italic;" | 9.7
|-
| Pregnancy
|
| 7
|-
| style="font-style: italic;" | Pregnancy and factor V leiden heterozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 35
|-
| Cancer
|
| 5
|-
| History of venous thrombosis
|
| 50
|}
Data were extracted from multiple sources.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref><ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref><ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>

==Prognosis==
The prognosis depends on the underlying thrombophilia as each form has a different associated thrombotic risk.

Patients who develop multiple or atyplical clots, arterial thrombosis, or life-threatening thrombosis have worse prognosis.

Thrombophilias generally associated with worse prognosis include:
*[[Antiphospholipid Syndrome]]
*[[Paroxysmal nocturnal hemoglobinuria]]
*Antithrombin III deficiency
*[[Factor V Leiden]] homozygosity

Certain thrombophilic conditions are high risk and require consideration for lifelong [[anticoagulation]]. In these cases, expert consultation is recommended.

{| class="wikitable"
! style="font-weight: bold;" | Possible indications for lifelong/prophylactic anticoagulation
|-
| Antiphospholipid syndrome
|-
| Paroxysmal nocturnal hemoglobinuria
|-
| Recurrent thrombosis regardless of underlying thrombophilia
|-
| History of life-threatening thrombosis or atypical locations
|-
| Malignancy with history of thrombosis
|}

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia medical therapy

2016-07-21T19:32:38Z

Asiri Saumya Ediriwickrema: update

__NOTOC__

{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}
==Overview==
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

==Medical Therapy==
*The 2016 guidelines from the [https://www.chestnet.org American College of Chest Physicians (ACCP)] recommend that patients with provoked venous thrombosis from reversible risk factors should receive 3-6 months of anticoagulation<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
***Response to anticoagulation can be monitored clinically, with repeat ultrasongraphy for [[Deep_vein_thrombosis|deep vein thrombosis]] or measuring [[D-dimer]] levels after treatment
*The 2016 guidelines from the ACCP recommend that direct oral anticoagulants (DOACs), including [[Direct_Xa_inhibitor|direct Xa inhibitors]] and [[Direct_thrombin_inhibitor|direct thrombin inhibitors]], be used for long term treatment of most patients<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
:*Important exceptions include:
:**Pregnancy<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
:**Renal insufficiency
:**Malignancy<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
*[[Low_molecular_weight_heparin|Low molecular weight heparin]] is recommended for anticoagulation for the following acquired thrombophilias:
**'''Post-surgery prophylaxis'''<ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
***The duration of anticoagulation after surgery is variable. Most clinical trials have evaluated anticoagulation for 10-35 days
***General recommendations for thrombophrophylaxis is 7-10 days for standard risk patients and 10-35 days for higher risk patients as described in the algorithims below and for patients undergoing abdominal and pelvic surgeries for gynecologic malginancies<ref name="pmid20409525">{{cite journal| author=Muntz J| title=Duration of deep vein thrombosis prophylaxis in the surgical patient and its relation to quality issues. | journal=Am J Surg | year= 2010 | volume= 200 | issue= 3 | pages= 413-21 | pmid=20409525 | doi=10.1016/j.amjsurg.2009.05.045 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20409525 }} </ref>
***DOACs may be considered as agents for extended thromboprophylaxis after [[Deep_vein_thrombosis_landmark_trials_in_prevention|total hip replacement and total knee replacement]].
**'''Pregnancy and postpartum'''<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
***Patients who develop acute thrombosis during pregnancy should be anticoagulated for the remainder of the their pregnancy and 6 weeks postpartum for a minimum of 3 months
***A similar duration of anticoagulation is recommended for patients with high risk thrombophilias as described in the algorithims below
**'''Malignancy'''<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
**Alternative agents include [[Warfarin]] and [[Fondaparinux]]

'''Treatment algorithms for both acquired and inherited thrombophilias are presented below:'''
*Thromboprophylaxis or indefinate anticoagulation may be required for certain inherited thrombophilias

[[Image: Thrombophilia_Management_Thrombosis.jpg|thumb|center|600px|Management of acute thrombosis in patients with inherited thrombophilias]]

[[Image: Thrombophilia_Inherited_Management.jpg|thumb|center|500px|Management of asymptomatic patients with inherited thrombophilias]]

[[Image: Thrombophilia_Acquired_Management.jpg|thumb|center|500px|Management of patients with acquired thrombophilias]]

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]

Thrombophilia overview

2016-07-21T19:16:17Z

Asiri Saumya Ediriwickrema: /* Risk Factors */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
'''Thrombophilia''' is a complex condition which increases the risk of [[thrombosis]] or thromboembolic disease. The predisposition to [[thrombus|clotting]], or '''thrombotic risk''', can be multi-factorial, and is due to an abnormality in [[coagulation]] described as '''hypercoagulability'''. Hypercoagulability is a component of [[Virchow's_triad|Virchow's Triad]], which by itself or in synergy with '''stasis''' or '''trauma''' can predispose to clot formation. The thrombotic risk associated with thrombophilic states is variable and depends on the underlying coagulopathy. Thrombophilias are classified as either inherited or a primary hypercoagulable state, acquired or a secondary hypercoagulable state, or mixed/unknown. [[Factor V Leiden]] and '''[[prothrombin]] gene mutations''' are the most common forms of inherited hypercoagulable states. Patients with thrombophilia can have a family history of [[thrombosis]], or present with frequent or unprovoked blood clots (primarily as [[deep vein thrombosis]] or [[pulmonary embolism]]), thrombosis at a young age, or blood clots in multiple or unusual sites.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis. Springer; 2014.</ref> [[Thrombophilia screening|Thrombophilia screening]] is controversial, but may aid in managing the initiation and duration of [[anticoagulation]] in affected patients and primary prevention in relatives.

==Historical Perspective==
Rudolf Virchow described hypercoagulability in the mid 1800s, however, it was not until 1965 that the first descriptions of inherited thrombophilia were published.<ref name="pmid7997003">{{cite journal| author=Schafer AI| title=Hypercoagulable states: molecular genetics to clinical practice. | journal=Lancet | year= 1994 | volume= 344 | issue= 8939-8940 | pages= 1739-42 | pmid=7997003 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7997003 }} </ref><ref name="pmid14347873">{{cite journal| author=EGEBERG O| title=INHERITED ANTITHROMBIN DEFICIENCY CAUSING THROMBOPHILIA. | journal=Thromb Diath Haemorrh | year= 1965 | volume= 13 | issue= | pages= 516-30 | pmid=14347873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14347873 }} </ref><ref name="pmid4956920">{{cite journal| author=Beck EA, Charache P, Jackson DP| title=A new inherited coagulation disorder caused by an abnormal fibrinogen ('fibrinogen Baltimore'). | journal=Nature | year= 1965 | volume= 208 | issue= 5006 | pages= 143-5 | pmid=4956920 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4956920 }} </ref> Later, in the 1990s, the more common mutations associated with primary hypercoagulable states were identified.<ref name="pmid8164741">{{cite journal| author=Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al.| title=Mutation in blood coagulation factor V associated with resistance to activated protein C. | journal=Nature | year= 1994 | volume= 369 | issue= 6475 | pages= 64-7 | pmid=8164741 | doi=10.1038/369064a0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8164741 }} </ref><ref name="pmid8916933">{{cite journal| author=Poort SR, Rosendaal FR, Reitsma PH, Bertina RM| title=A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. | journal=Blood | year= 1996 | volume= 88 | issue= 10 | pages= 3698-703 | pmid=8916933 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8916933 }} </ref>

==Classification==
Thrombophilias may be classified into three groups: '''inherited or primary hypercoagulable states''', '''acquired or secondary hypercoagulable states''', or '''mixed/unknown'''. Certain conditions are associated with greater thrombotic risks and both venous and arterial clots.

==Pathophysiology==
The pathogenesis of thrombophilia is multi-factorial. It is characterized by hypercoagulability, which by itself or in synergy with '''endothelial injury''' or '''stasis''' ([[Virchow's_triad|Virchow's Triad]]) can predispose to [[thrombus|clot formation]]. Multiple [[Thrombophilia_classification|genetic mutations and predisposing conditions]] have been associated with the increased risk of [[thrombosis]] due to abnormalities in the [[coagulation]] cascade.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The most common genes involved in the pathogenesis of acquired thrombophilias are [[Factor V Leiden]] and '''[[prothrombin]] gene mutations'''.

==Causes==
Thrombophilia may be caused by either [[Thrombophilia_classification|acquired, inherited, or, more commonly, a combination of both conditions]]. The most frequent forms of inherited thrombophilia are Factor V Leiden (20-50% prevalence in patients with recurrent venous thrombosis) and prothrombon G20210A (5-20% prevalence in patients with recurrent venous thrombosis).<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

==Differentiating Inherited Thrombophilia from other Diseases==
Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]. Inherited thrombophilias should be suspected in patients with the certain [[Thrombophilia_history_and_symptoms|clinical presentations]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> [[Thrombophilia screening|Screening]] for inherited thrombophilias is controversial and should be performed in the appropriate clinical context.<ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

==Epidemiology and Demographics==
Due to the multitude and complexity of inherited thrombophilias, the true [[prevalence]] is unknown, and current data may be providing an underestimate. Comparison among different epidemiologic studies becomes difficult due to variation in study design and inclusion criteria. Prevalence of common inherited thrombophilias is variable among both healthy patients and patients with recurrent [[thrombosis]]. According to epidemiologic and modeling studies obtained from certain sources, the prevalence of inherited thrombophilias was estimated to be between 0.01-7% in caucasians.<ref name="pmid26780744">{{cite journal| author=Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M et al.| title=Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 154-64 | pmid=26780744 | doi=10.1007/s11239-015-1316-1 | pmc=4715840 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780744 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> In certain studies, the prevalence of inherited thrombophilias, specifically, '''activated protein C resistance''' and '''prothrombin G20210A''', rises to approximately 10-60% in patients with documented venous thrombosis compared to less than 10% among controls.<ref name="pmid9669991">{{cite journal| author=Margaglione M, Brancaccio V, Giuliani N, D'Andrea G, Cappucci G, Iannaccone L et al.| title=Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant. | journal=Ann Intern Med | year= 1998 | volume= 129 | issue= 2 | pages= 89-93 | pmid=9669991 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9669991 }} </ref><ref name="pmid7877648">{{cite journal| author=Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP| title=Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. | journal=N Engl J Med | year= 1995 | volume= 332 | issue= 14 | pages= 912-7 | pmid=7877648 | doi=10.1056/NEJM199504063321403 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7877648 }} </ref><ref name="pmid7902898">{{cite journal| author=Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM| title=Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. | journal=Lancet | year= 1993 | volume= 342 | issue= 8886-8887 | pages= 1503-6 | pmid=7902898 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7902898 }} </ref> The incidence of inherited thrombophilia in incident venous thrombosis is approximately 150-840 per 100,000 person years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref> The incidence of inherited thrombophilia in recurrent venous thrombosis is approximately 3,500-10,500 per 100,000 person-years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

===Age===
Patients of all age groups may develop thrombophilias. Acquired thrombophilias are more commonly observed among elderly patients (age > 60) as age is a risk factor for thrombosis. Inherited thrombophilias can be seen among young patients aged <40-55 years old.

===Gender===
Epidemiologic studies have provided mixed results regarding the effect of gender on venous thrombosis. Certain groups observed increased risk of thrombosis in younger females and older males, whereas other groups found similar frequencies in both genders.<ref name="pmid12814979">{{cite journal| author=White RH| title=The epidemiology of venous thromboembolism. | journal=Circulation | year= 2003 | volume= 107 | issue= 23 Suppl 1 | pages= I4-8 | pmid=12814979 | doi=10.1161/01.CIR.0000078468.11849.66 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12814979 }} </ref> A prospective follow up study performed by Christiansen et al, revealed an age corrected hazard ratio of 2.7 of recurrent thrombosis in male patients with inherited thrombophilias compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref> In patients with inherited thrombophilias, a prospective follow up study performed by Christiansen et al revealed an age corrected hazard ratio of 2.7 for recurrent thrombosis in male patients compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref>

===Race===
The factor V leiden G1691A and prothrombin G20210A mutations are exceedingly rare in non-white populations.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

==Risk Factors==
The most common risk factors in the development of acquired thrombophlias are [[trauma]], [[surgery]], [[immobility]], pregnancy, [[oral contraceptives]], [[hormone replacement therapy]], and age. Common risk factors for the development of inherited thrombophilias are a family history of [[thrombosis]] at an early age or a family history of inherited thrombophilia. Common genetic risk factors in the development of inherited thrombophilias are mutations in [[Factor_V_Leiden|Factor V Leiden]] and [[prothrombin]] G20210A.

== Natural History, Complications and Prognosis==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref> If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) is low (<0.06%) .<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref> Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref> Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref> OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref> Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

== Diagnosis ==
===Diagnostic Criteria===
The diagnosis of an inherited thrombophilia is made with specific [[Thrombophilia_laboratory_findings|laboratory tests]] for each inherited condition.

=== Symptoms ===
Common symptoms of thrombophilias may include symptoms of [[Deep venous thrombosis]], [[Pulmonary embolus]], and superficial venous thrombosis.

=== Physical Examination ===
Physical examination of patients with thrombophilia is usually remarkable for signs of [[Deep_vein_thrombosis_physical_examination|deep venous thrombosis]], [[Pulmonary_embolism_physical_examination|pulmonary thrombosis]], [[Renal_vein_thrombosis|renal vein thrombosis]], [[Cerebral_venous_sinus_thrombosis_physical_examination|cerebral vein thrombosis]], [[Superficial_vein_thrombosis|superficial vein thrombosis]], arterial thrombosis, [[Portal_hypertension_physical_examination|portal hypertension]] which can be sign of [https://en.wikipedia.org/wiki/Portal_vein_thrombosis| portal vein thrombosis], [[Warfarin_necrosis|warfarin skin necrosis]], or [https://en.wikipedia.org/wiki/Livedo_reticularis livedo reticularis].<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

=== Screening ===
According to the American Society of Hematology, screening for inherited thrombophilias in adult patients with venous [[thrombosis]] in the setting of major transient risk factors which include surgery, trauma, or prolonged immobility is not recommended.<ref name="pmid24319155">{{cite journal| author=Hicks LK, Bering H, Carson KR, Kleinerman J, Kukreti V, Ma A et al.| title=The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. | journal=Hematology Am Soc Hematol Educ Program | year= 2013 | volume= 2013 | issue= | pages= 9-14 | pmid=24319155 | doi=10.1182/asheducation-2013.1.9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24319155 }} </ref> However, given the [[Thrombophilia_natural_history,_complications_and_prognosis|associated risks]] for recurrent thrombosis, patients who have significant risk factors including a positive family history or concurrent treatment with hormonal therapies should seek expert consultation.

=== Laboratory Findings ===
Laboratory findings consistent with the diagnosis of inherited thrombophilias include specific [[Thrombophilia_laboratory_findings|laboratory findings]] associated with each inherited thrombophilia.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

===Imaging Findings===
[[Ultrasound|Ultrasongraphy]], [https://en.wikipedia.org/wiki/Computed_tomography_angiography| computed tomography angiography (CTA or CT Angiography)], [https://en.wikipedia.org/wiki/Magnetic_resonance_angiography| magnetic resonance angiography (MRA or MR Angiography)] and [[Angiogram|projectional angiography]] may be diagnostic of acute thrombosis, which is associated with the diagnosis of thrombophilia.

== Treatment ==
=== Medical Therapy ===
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

=== Surgery ===
Surgery is not required for treatment for thrombophilia. [[IVC_filter|IVC filter]] placement may be indicated if the patient has contraindications to or complications from [[anticoagulation]], recurrent thrombosis on anticoagulation, or failure to acheive therapeutic anticoagulation levels.<ref> Inferior Vena Cava Filters. Medscape (2015). URL Accessed on July 17, 2016</ref>

=== Prevention ===
[[Thrombophilia_medical_therapy|Prophylaxis]] with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|certain scenarios]]. Once diagnosed and successfully treated, patients with thrombophilia are followed-up routinely to monitor anticoagulation and clinically if thrombosis recurrs

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Hematology]]
[[Category:Primary care]]

Thrombophilia risk factors

2016-07-21T19:15:17Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
The most common risk factors in the development of acquired thrombophlias are [[trauma]], [[surgery]], [[immobility]], pregnancy, [[oral contraceptives]], [[hormone replacement therapy]], and age. Common risk factors for the development of inherited thrombophilias are a family history of [[thrombosis]] at an early age or a family history of inherited thrombophilia. Common genetic risk factors in the development of inherited thrombophilias are mutations in [[Factor_V_Leiden|factor V leiden]] and [[prothrombin]] G20210A.

==Risk Factors==
*The most common risk factors in the development of acquired thrombophlias are the following:
**Trauma
**Surgery
**Immobility
**Age
**Hormones
***Pregnancy
***[[Oral_contraceptive|Oral contraceptive pills]]
***[[Hormone_replacement_therapy|Hormone therapy]]

Common risk factors for the development of inherited thrombophilias are a family history of thrombosis at an early age or a family history of inherited thrombophilia.

Common genetic risk factors in the development of inherited thrombophilias are mutations in [[Factor_V_Leiden|Factor V Leiden]] and [[Prothrombin G20210A]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

Please see [[Thrombophilia classification|thrombophilia classification]] for a list conditions associated with acquired thrombophilias, and to the page on [[Thrombophilia_causes|causes of thrombophilia by organ system]].

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia differential diagnosis

2016-07-21T19:04:29Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
Thrombophilia is a prothrombotic state due to an underlying process. Inherited thrombophilias must be differentiated from acquired thrombophilias, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]. Inherited thrombophilias should be suspected in patients with the certain [[Thrombophilia_history_and_symptoms|clinical presentations]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> [[Thrombophilia screening|Screening]] for inherited thrombophilias is controversial and should be performed in the appropriate clinical context.<ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

==Differential Diagnosis==
*Thrombophilia is a prothrombotic state due to an underlying process
*Inherited thrombophilias must be differentiated from acquired thrombophilias, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]
**The most common inherited thrombophilias include [[Factor V Leiden]] and [http://emedicine.medscape.com/article/209742-overview Prothrombin G20210A]
**The most common acquired thrombophilic states include [[surgery]], [[trauma]], or prolonged [[immobility]]
**Refer to the [[Thrombophilia_classification|classification section]] for a complete description of various hypercoagulable states
*Inherited thrombophilias should be suspected in patients with the following clinical presentations:<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>
**Family history of thrombosis, especially at an early age (< 45 years)
**Unprovoked thrombosis at an early age (<40-55 for venous thrombosis and <50-55 for arterial thrombosis)
**Recurrent thrombosis including [[Deep venous thrombosis]], [[Pulmonary embolus]], or superficial venous thrombosis
**Thrombosis at multiple sites, or unusual locations including in cerebral, hepatic, portal, mesenteric, and renal veins
**Thrombosis in arteries with the abscence of [[Peripheral_arterial_disease|arterial disease]]
**History of fetal loss
**History of [[Warfarin_necrosis|warfarin skin necrosis]]

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia natural history, complications and prognosis

2016-07-21T05:47:40Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref>

==Natural History==
* Refer to the [[Thrombophilia_history_and_symptoms|clinical symptoms]] section regarding early clinical features of patients with thrombophilia.
* If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) (<0.06%) is low.<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref>
* Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref>
* Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref>
* OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>
* Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

==Complications==
* The primary complication of thrombophilia is the development of [[Thrombus|blood clots]]
* Patients with primary hypercoagulable states develop thrombosis mostly in the settting of aquired risk factors which include [[trauma]], [[surgery]], [[immobility]], pregnancy and use of OCPs.
* [[Deep vein thrombosis]] and [[pulmonary embolus]] are the most common complications.

'''The risk of future thrombosis in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" |Thrombophilic state
! style="font-weight: bold;" |Thrombotic risk<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref>
|-
| Trauma/General surgery
| Modest
|-
| Age > 60
| Modest
|-
| Immobilization
| Modest
|-
| Pregnancy
| Modest
|-
| Hormone therapies
| Modest
|-
| Factor V Leiden heterozygosity
| Modest
|-
| Prothrombin mutation
| Modest
|-
| Homocysteinemia
| Modest
|-
| Increased factor VIII levels
| Modest
|-
| Increased factor IX levels
| Modest
|-
| Increased factor XI levels
| Modest
|-
| Protein C and S deficiency
| Intermediate
|-
| Dysfibrogenemia
| Intermediate
|-
| Malignancy
| High
|-
| APLS/Lupus anticoagulant
| High
|-
| Myeloproliferative disorders/hyperviscosity
| High
|-
| PNH
| High
|-
| Orthopedic surgery
| High
|-
| Antithrombin deficiency
| High
|-
| Factor V Leiden homozygosity
| High
|-
|}

'''The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" | Thrombophilic state
! style="font-weight: bold;" | Annual Incidence (%)
! style="font-weight: bold;" | Relative Risk
|-
| Normal
| 0.008
| 1
|-
| Factor V leiden heterozygous
| 0.06
| 3-10
|-
| Factor V leiden homozygous
| 0.5-1
| 80
|-
| Prothrombin G20210A
| 0.02
| 1-5
|-
| Oral contraceptive (OCP)
| 0.03
| 4
|-
| style="font-style: italic;" | OCP and factor V leiden heterozygous
| style="font-style: italic;" | 0.3
| style="font-style: italic;" | 35
|-
| style="font-style: italic;" | OCP and factor V leiden homozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 100
|-
| style="font-style: italic;" | OCP and prothrombin G20210A
| style="font-style: italic;" |
| style="font-style: italic;" | 16
|-
| style="font-style: italic;" | OCP and protein C/S, or antithrombin III deficiency
| style="font-style: italic;" |
| style="font-style: italic;" | 9.7
|-
| Pregnancy
|
| 7
|-
| style="font-style: italic;" | Pregnancy and factor V leiden heterozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 35
|-
| Cancer
|
| 5
|-
| History of venous thrombosis
|
| 50
|}
Data were extracted from multiple sources.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref><ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref><ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>

==Prognosis==
*The prognosis depends on the underlying thrombophilia as each form has a different associated thrombotic risk
*Certain thrombophilic conditions are high risk and require consideration for lifelong anticoagulation. In these cases, expert consultation is recommended.

{| class="wikitable"
! style="font-weight: bold;" | Possible indications for lifelong/prophylactic anticoagulation
|-
| Antiphospholipid syndrome
|-
| Paroxysmal nocturnal hemoglobinuria
|-
| Recurrent thrombosis regardless of underlying thrombophilia
|-
| History of life-threatening thrombosis or atypical locations
|-
| Malignancy with history of thrombosis
|}

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia risk factors

2016-07-21T05:38:04Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
The most common risk factors in the development of acquired thrombophlias are trauma, surgery, immobility, pregnancy, estrogen therapy, and age. The most common risk factors in the development of inherited thrombophilias are genetic mutations in factor V leiden and prothrombon G20210A.

==Risk Factors==
*The most common risk factors in the development of acquired thrombophlias are the following:
**Trauma
**Surgery
**Immobility
**Age
**Hormones
***Pregnancy
***[[Oral_contraceptive|Oral contraceptive pills]]
***[[Hormone_replacement_therapy|Hormone therapy]]

Common risk factors for the development of inherited thrombophilias are a family history of thrombosis at an early age or a family history of inherited thrombophilia.

Common genetic risk factors in the development of inherited thrombophilias are mutations in [[Factor V Leiden]] and [[Prothrombon G20210A]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

Please see [[Thrombophilia classification|thrombophilia classification]] for a list conditions associated with acquired thrombophilias, and to the page on [[Thrombophilia_causes|causes of thrombophilia by organ system]].

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia differential diagnosis

2016-07-21T04:11:37Z

Asiri Saumya Ediriwickrema: update

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]. Inherited thrombophilias should be suspected in patients with the certain [[Thrombophilia_history_and_symptoms|clinical presentations]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> [[Thrombophilia screening|Screening]] for inherited thrombophilias is controversial and should be performed in the appropriate clinical context.<ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

==Differential Diagnosis==
*Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]
**The most common inherited thrombophilias include [[Factor V Leiden]] and [http://emedicine.medscape.com/article/209742-overview Prothrombin G20210A]
**The most common acquired thrombophilic states include [[surgery]], [[trauma]], or prolonged [[immobility]]
**Refer to the [[Thrombophilia_classification|classification section]] for a complete description of various hypercoagulable states
*Inherited thrombophilias should be suspected in patients with the following clinical presentations:<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>
**Family history of thrombosis, especially at an early age (< 45 years)
**Unprovoked thrombosis at an early age (<40-55 for venous thrombosis and <50-55 for arterial thrombosis)
**Recurrent thrombosis including [[Deep venous thrombosis]], [[Pulmonary embolus]], or superficial venous thrombosis
**Thrombosis at multiple sites, or unusual locations including in cerebral, hepatic, portal, mesenteric, and renal veins
**Thrombosis in arteries with the abscence of [[Peripheral_arterial_disease|arterial disease]]
**History of fetal loss
**History of [[Warfarin_necrosis|warfarin skin necrosis]]

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia natural history, complications and prognosis

2016-07-21T02:43:05Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref>

==Natural History==
* Refer to the [[Thrombophilia_history_and_symptoms|clinical symptoms]] section regarding early clinical features of patients with thrombophilia.
* If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) (<0.06%) is low.<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref>
* Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref>
* Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref>
* OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>
* Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

==Complications==
* Patients with primary hypercoagulable states develop thrombotic complications mostly in the settting of aquired risk factors which include trauma, surgery, immobility, pregnancy and use of OCPs.
* [[Deep vein thrombosis]] and [[pulmonary embolus]] are the most common complications.

'''The risk of future thrombosis in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" |Thrombophilic state
! style="font-weight: bold;" |Thrombotic risk<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref>
|-
| Trauma/General surgery
| Modest
|-
| Age > 60
| Modest
|-
| Immobilization
| Modest
|-
| Pregnancy
| Modest
|-
| Hormone therapies
| Modest
|-
| Factor V Leiden heterozygosity
| Modest
|-
| Prothrombin mutation
| Modest
|-
| Homocysteinemia
| Modest
|-
| Increased factor VIII levels
| Modest
|-
| Increased factor IX levels
| Modest
|-
| Increased factor XI levels
| Modest
|-
| Protein C and S deficiency
| Intermediate
|-
| Dysfibrogenemia
| Intermediate
|-
| Malignancy
| High
|-
| APLS/Lupus anticoagulant
| High
|-
| Myeloproliferative disorders/hyperviscosity
| High
|-
| PNH
| High
|-
| Orthopedic surgery
| High
|-
| Antithrombin deficiency
| High
|-
| Factor V Leiden homozygosity
| High
|-
|}

'''The effect of concurrent hormone exposure on incident thrombosis and thrombotic risk in patients with thrombophilia:'''
{| class="wikitable"
! style="font-weight: bold;" | Thrombophilic state
! style="font-weight: bold;" | Annual Incidence (%)
! style="font-weight: bold;" | Relative Risk
|-
| Normal
| 0.008
| 1
|-
| Factor V leiden heterozygous
| 0.06
| 3-10
|-
| Factor V leiden homozygous
| 0.5-1
| 80
|-
| Prothrombin G20210A
| 0.02
| 1-5
|-
| Oral contraceptive (OCP)
| 0.03
| 4
|-
| style="font-style: italic;" | OCP and factor V leiden heterozygous
| style="font-style: italic;" | 0.3
| style="font-style: italic;" | 35
|-
| style="font-style: italic;" | OCP and factor V leiden homozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 100
|-
| style="font-style: italic;" | OCP and prothrombin G20210A
| style="font-style: italic;" |
| style="font-style: italic;" | 16
|-
| style="font-style: italic;" | OCP and protein C/S, or antithrombin III deficiency
| style="font-style: italic;" |
| style="font-style: italic;" | 9.7
|-
| Pregnancy
|
| 7
|-
| style="font-style: italic;" | Pregnancy and factor V leiden heterozygous
| style="font-style: italic;" |
| style="font-style: italic;" | 35
|-
| Cancer
|
| 5
|-
| History of venous thrombosis
|
| 50
|}
Data were extracted from multiple sources.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref><ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref><ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref>

==Prognosis==
*Certain thrombophilic conditions are high risk and require consideration for lifelong anticoagulation. In these cases, expert consultation is recommended.

{| class="wikitable"
! style="font-weight: bold;" | Possible indications for lifelong/prophylactic anticoagulation
|-
| Antiphospholipid syndrome
|-
| Paroxysmal nocturnal hemoglobinuria
|-
| Recurrent thrombosis regardless of underlying thrombophilia
|-
| History of life-threatening thrombosis or atypical locations
|-
| Malignancy with history of thrombosis
|}

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia secondary prevention

2016-07-20T19:58:47Z

Asiri Saumya Ediriwickrema: update

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
Secondary prevention strategies following acute thrombosis in patients with thrombophilia include [[anticoagulation]].

==Secondary Prevention==
Thromboprophylaxis with [[anticoagulation]] may be recommended for secondary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|high risk acquired and inherited thrombophilias]]:<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
*[[Antiphospholipid syndrome]]
*[[Paroxysmal nocturnal hemoglobinuria]] (PNH)
**[[Eculizumab]] is a monocolonal antibody used for treatment of PNH
*Recurrent [[thrombosis]]
*Unprovoked thrombus
*History of life threatening thrombus or thrombosis in atypical locations
*Multiple inherited thrombophilias
*Malignancy with history of thrombosis
*Concerning family history
*Male sex
Refer to the [[Thrombophilia_medical_therapy|medical therapy for thrombophilias]] section for more information.

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia primary prevention

2016-07-20T19:50:02Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Thrombophilia_medical_therapy|Thromboprophylaxis]] with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|high risk acquired and inherited thrombophilias]].

==Primary Prevention==
Thromboprophylaxis with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|high risk acquired and inherited thrombophilias]]:<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
*[[Antithrombin]] deficiency
*[[Zygosity|Homozygous or compound heterozygous]] mutations for the underlying thrombophilias
*Multiple inherited thrombophilias
*Family history of [[thrombosis]] at a young age
*Post [[Orthopedic_surgery|orthopedic surgery]]
*Post abdominal or pelvic surgery for gynecologic malignancies
Refer to the [[Thrombophilia_medical_therapy|medical therapy section]] for additional information.

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia primary prevention

2016-07-20T19:49:09Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Thrombophilia_medical_therapy|Thromboprophylaxis]] with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|high risk acquired and inherited thrombophilias]].

==Primary Prevention==
Thromboprophylaxis with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|high risk acquired and inherited thrombophilias]]:<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
*[[Antithrombin]] deficiency
*[[Zygosity|Homozygous or compound heterozygous]] mutations for the underlying thrombophilias
*Multiple thrombophilias
*Family history of [[thrombosis]] at a young age
*Post [[Orthopedic_surgery|orthopedic surgery]]
*Post abdominal or pelvic surgery for gynecologic malignancies
Refer to the [[Thrombophilia_medical_therapy|medical therapy section]] for additional information.

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia primary prevention

2016-07-20T19:45:28Z

Asiri Saumya Ediriwickrema: update

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Thrombophilia_medical_therapy|Thromboprophylaxis]] with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|high risk acquired and inherited thrombophilias]].

==Primary Prevention==
Thromboprophylaxis with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|high risk acquired and inherited thrombophilias]].<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
*[[Antithrombin]] deficiency
*[[Zygosity|Homozygous or compound heterozygous]] mutations for the underlying thrombophilias
*Multiple thrombophilias
*Family history of [[thrombosis]] at a young age
*Post [[Orthopedic_surgery|orthopedic surgery]]
*Post abdominal or pelvic surgery for gynecologic malignancies
Refer to the [[Thrombophilia_medical_therapy|medical therapy section]] for additional information.

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia primary prevention

2016-07-20T19:40:57Z

Asiri Saumya Ediriwickrema:

Thrombophilia primary prevention

2016-07-20T19:40:24Z

Asiri Saumya Ediriwickrema: update

Thrombophilia medical therapy

2016-07-20T19:25:39Z

Asiri Saumya Ediriwickrema:

__NOTOC__

{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}
==Overview==
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

==Medical Therapy==
*Patients with provoked venous thrombosis from reversible risk factors should receive 3-6 months of anticoagulation<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
***Response to anticoagulation can be monitored clinically, with repeat ultrasongraphy for [[Deep_vein_thrombosis|deep vein thrombosis]] or measuring [[D-dimer]] levels after treatment
*Direct oral anticoagulants (DOACs), including [[Direct_Xa_inhibitor|direct Xa inhibitors]] and [[Direct_thrombin_inhibitor|direct thrombin inhibitors]], should be used for long term treatment of most patients<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
:*Important exceptions include:
:**Pregnancy<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
:**Renal insufficiency
:**Malignancy<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
*[[Low_molecular_weight_heparin|Low molecular weight heparin]] is recommended for anticoagulation for the following acquired thrombophilias:
**'''Post-surgery prophylaxis'''<ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
***The duration of anticoagulation after surgery is variable. Most clinical trials have evaluated anticoagulation for 10-35 days
***General recommendations for thrombophrophylaxis is 7-10 days for standard risk patients and 10-35 days for higher risk patients as described in the algorithims below and for patients undergoing abdominal and pelvic surgeries for gynecologic malginancies<ref name="pmid20409525">{{cite journal| author=Muntz J| title=Duration of deep vein thrombosis prophylaxis in the surgical patient and its relation to quality issues. | journal=Am J Surg | year= 2010 | volume= 200 | issue= 3 | pages= 413-21 | pmid=20409525 | doi=10.1016/j.amjsurg.2009.05.045 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20409525 }} </ref>
***DOACs may be considered as agents for extended thromboprophylaxis after [[Deep_vein_thrombosis_landmark_trials_in_prevention|total hip replacement and total knee replacement]].
**'''Pregnancy and postpartum'''<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
***Patients who develop acute thrombosis during pregnancy should be anticoagulated for the remainder of the their pregnancy and 6 weeks postpartum for a minimum of 3 months
***A similar duration of anticoagulation is recommended for patients with high risk thrombophilias as described in the algorithims below
**'''Malignancy'''<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
**Alternative agents include [[Warfarin]] and [[Fondaparinux]]
*'''Treatment algorithms for both acquired and inherited thrombophilias are presented below:'''
**Thromboprophylaxis or indefinate anticoagulation may be required for certain inherited thrombophilias.

[[Image: Thrombophilia_Management_Thrombosis.jpg|thumb|center|700px|Management of acute thrombosis in patients with inherited thrombophilias]]

[[Image: Thrombophilia_Inherited_Management.jpg|thumb|center|500px|Management of asymptomatic patients with inherited thrombophilias]]

[[Image: Thrombophilia_Acquired_Management.jpg|thumb|center|500px|Management of patients with acquired thrombophilias]]

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]

File:Thrombophilia Acquired Management.jpg

2016-07-20T19:22:52Z

Asiri Saumya Ediriwickrema: Asiri Saumya Ediriwickrema uploaded a new version of File:Thrombophilia Acquired Management.jpg

File:Thrombophilia Management Thrombosis.jpg

2016-07-20T19:09:50Z

Asiri Saumya Ediriwickrema: Asiri Saumya Ediriwickrema uploaded a new version of File:Thrombophilia Management Thrombosis.jpg

Thrombophilia differential diagnosis

2016-07-20T18:56:19Z

Asiri Saumya Ediriwickrema: update

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]. Inherited thrombophilias should be suspected in patients with the certain [[Thrombophilia_history_and_symptoms|clinical presentations]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> [[Thrombophilia screening|Screening]] for inherited thrombophilias is controversial and should be performed in the appropriate clinical context.<ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

==Differential Diagnosis==
*Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]
*Inherited thrombophilias should be suspected in patients with the following clinical presentations:<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>
**Family history of thrombosis, especially at an early age (< 45 years)
**Unprovoked thrombosis at an early age (<40-55 for venous thrombosis and <50-55 for arterial thrombosis)
**Recurrent thrombosis including [[Deep venous thrombosis]], [[Pulmonary embolus]], or superficial venous thrombosis
**Thrombosis at multiple sites, or unusual locations including in cerebral, hepatic, portal, mesenteric, and renal veins
**Thrombosis in arteries with the abscence of [[Peripheral_arterial_disease|arterial disease]]
**History of fetal loss
**History of [[Warfarin_necrosis|warfarin skin necrosis]]

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia classification

2016-07-20T18:45:38Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}}; {{AE}} {{asiri}}

==Overview==
Thrombophilia may be classified into three subtypes: '''inherited or primary hypercoagulable states''', '''acquired or secondary hypercoagulable states''', and '''mixed/unknown'''.<ref name=Hoffman1>Hoffman R, Benz EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice: Elsevier Science Health Science Division; 2004.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

==Classification==
*Thrombophilia may be classified into three subtypes:<ref name=Hoffman1>Hoffman R, Benz EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice: Elsevier Science Health Science Division; 2004.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>
:*Inherited thrombophilia or primary hypercoagulable state
:*Acquired thrombophilia or secondary hypercoagulable state
:*Mixed/Unknown
*Different thrombophilic states are associated with venous or both venous and arterial clots.

{| class="wikitable"
! colspan="3" style="text-align: center; font-weight: bold;" | Thrombophilia Classification
|-
| style="font-weight: bold; font-style: italic;" | Inherited (Primary)
| style="font-weight: bold; font-style: italic;" | Acquired (Secondary)
| style="font-weight: bold; font-style: italic;" | Mixed/Unknown
|-
| [[Activated protein C resistance]] ([[Factor V Leiden]])
| [[Age]]
| [[Hyperhomocysteinemia]]
|-
| [[Prothrombin]] gene mutation (Prothrombin G20210A)
| [[Immobilization]]
| APC resistance unrelated to Factor V Leiden.
|-
| [[Antithrombin deficiency]]
| [[Trauma]]/major surgery
| Increased [[Factor VIII]] levels
|-
| [[Protein C deficiency|Protein C]] and [[Protein S deficiency]]
| [[Orthopedic surgery]]
| Increased [[Factor XI]] levels
|-
| Dysfibrinogenemia
| [[Malignancy]]
| Increased [[Factor IX]] levels
|-
| Non-O [[blood type]]
| [[Myeloproliferative neoplasm|Myeloproliferative disorders]] ([[polycythemia vera]], [[essential thrombocythemia]], [[hyperviscosity]])
| Increased levels of [[thrombin-activatable fibrinolysis inhibitor]] (TAFI)
|-
|
| [[Pregnancy]]
| Decreased levels of free [[tissue factor pathway inhibitor]] (TFPI)
|-
|
| [[Estrogen]] and [[testosterone]] ([[oral contraceptive]]s, [[hormone replacement therapy]], and [[selective estrogen receptor modulator]])
|
|-
|
| [[Obesity]]
|
|-
|
| [[Heart Failure]]
|
|-
|
| [[Cirrhosis]]
|
|-
|
| [[Chronic renal disease]], [[Nephrotic syndrome]]
|
|-
|
| [[Antiphospholipid syndrome]] (APLS) or [[lupus anticoagulant]]
|
|-
|
| [[Heparin-induced thrombocytopenia]] (HIT)
|
|-
|
| [[Disseminated intravascular coagulopathy]] (DIC)
|
|-
|
| [[Paroxysmal nocturnal hemoglobinuria]] (PNH)
|
|-
|
| Autoimmune disorders ([[Vasculitis]], [[Celiac disease]], [[Inflammatory bowel disease]])
|
|-
|
| [[Thrombotic microangiopathy]]
|
|-
|
| [[Sickle cell disease]]
|
|-
|
| Drug related (chemotherapies including L-aspariginase, [[mitomycin]]; infusion of clotting factors including [[prothrombin]] complex concentrates, [[cryoprecipitate]]; drugs including [[hydralazine]], [[procainamide]], or [[phenothiazines]] can promote lupus anticoagulant formation)
|
|}

{| class="wikitable"
! style="text-align: center;" | Thrombophilic states associated with arterial clots
|-
| style="text-align: center;" | APLS and lupus anticoagulant
|-
| style="text-align: center;" | HIT
|-
| style="text-align: center;" | DIC
|-
| style="text-align: center;" | PNH
|-
| style="text-align: center;" | [[Cold_agglutinin_disease|Cold agglutinins]] (associated with [[Mycoplasma_pneumonia|mycoplasma infections]])
|-
| style="text-align: center;" | Vasculitis
|-
| style="text-align: center;" | Hyperhomocysteinemia
|}

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Hematology]]
[[Category:FinalQCRequired]]

Thrombophilia classification

2016-07-20T18:35:30Z

Asiri Saumya Ediriwickrema: /* Classification */

__NOTOC__
{{Thrombophilia}}
{{CMG}}; {{AE}} {{asiri}}

==Overview==
Thrombophilia may be classified into three subtypes: '''inherited or primary hypercoagulable states''', '''acquired or secondary hypercoagulable states''', and '''mixed/unknown'''.<ref name=Hoffman1>Hoffman R, Benz EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice: Elsevier Science Health Science Division; 2004.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

==Classification==
*Thrombophilia may be classified into three subtypes:<ref name=Hoffman1>Hoffman R, Benz EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice: Elsevier Science Health Science Division; 2004.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>
:*Inherited thrombophilia or primary hypercoagulable state
:*Acquired thrombophilia or secondary hypercoagulable state
:*Mixed/Unknown
*Different thrombophilic states are associated with venous or both venous and arterial clots.

{| class="wikitable"
! colspan="3" style="text-align: center; font-weight: bold;" | Thrombophilia Classification
|-
| style="font-weight: bold; font-style: italic;" | Inherited (Primary)
| style="font-weight: bold; font-style: italic;" | Acquired (Secondary)
| style="font-weight: bold; font-style: italic;" | Mixed/Unknown
|-
| [[Activated protein C resistance]] ([[Factor V Leiden]])
| [[Age]]
| [[Hyperhomocysteinemia]]
|-
| [[Prothrombin]] gene mutation (Prothrombin G20210A)
| [[Immobilization]]
| APC resistance unrelated to Factor V Leiden.
|-
| [[Antithrombin deficiency]]
| [[Trauma]]/major surgery
| Increased [[Factor VIII]] levels
|-
| [[Protein C deficiency|Protein C]] and [[Protein S deficiency]]
| [[Orthopedic surgery]]
| Increased [[Factor XI]] levels
|-
| Dysfibrinogenemia
| [[Malignancy]]
| Increased [[Factor IX]] levels
|-
| Non-O [[blood type]]
| [[Myeloproliferative neoplasm|Myeloproliferative disorders]] ([[polycythemia vera]], [[essential thrombocythemia]], [[hyperviscosity]])
| Increased levels of [[thrombin-activatable fibrinolysis inhibitor]] (TAFI)
|-
|
| [[Pregnancy]]
| Decreased levels of free [[tissue factor pathway inhibitor]] (TFPI)
|-
|
| [[Estrogen]] and [[testosterone]] ([[oral contraceptive]]s, [[hormone replacement therapy]], and [[selective estrogen receptor modulator]])
|
|-
|
| [[Obesity]]
|
|-
|
| [[Heart Failure]]
|
|-
|
| [[Cirrhosis]]
|
|-
|
| [[Chronic renal disease]], [[Nephrotic syndrome]]
|
|-
|
| [[Antiphospholipid syndrome]] (APLS) or [[lupus anticoagulant]]
|
|-
|
| [[Heparin-induced thrombocytopenia]] (HIT)
|
|-
|
| [[Disseminated intravascular coagulopathy]] (DIC)
|
|-
|
| [[Paroxysmal nocturnal hemoglobinuria]] (PNH)
|
|-
|
| Autoimmune disorders ([[Vasculitis]], [[Celiac disease]], [[Inflammatory bowel disease]])
|
|-
|
| [[Thrombotic microangiopathy]]
|
|-
|
| [[Sickle cell disease]]
|
|-
|
| Drug related (chemotherapies including L-aspariginase, [[mitomycin]]; infusion of clotting factors including [[prothrombin]] complex concentrates, [[cryoprecipitate]]; drugs including [[hydralazine]], [[procainamide]], or [[phenothiazines]] can promote lupus anticoagulant formation)
|
|}

{| class="wikitable"
! style="text-align: center;" | Thrombophilic states associated with arterial clots
|-
| style="text-align: center;" | APLS and lupus anticoagulant
|-
| style="text-align: center;" | HIT
|-
| style="text-align: center;" | DIC
|-
| style="text-align: center;" | PNH
|-
| style="text-align: center;" | Cold agglutinins (associated with mycoplasma infections)
|-
| style="text-align: center;" | Vasculitis
|-
| style="text-align: center;" | Hyperhomocysteinemia
|}

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Hematology]]
[[Category:FinalQCRequired]]

Thrombophilia causes

2016-07-19T05:41:20Z

Asiri Saumya Ediriwickrema: /* Inherited */

__NOTOC__

{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
Thrombophilia may be caused by either [[Thrombophilia_classification|acquired, inherited, or, more commonly, a combination of both conditions]]. The most frequent forms of inherited thrombophilia are Factor V Leiden (20-50% prevalence in patients with recurrent venous thrombosis) and prothrombon G20210A (5-20% prevalence in patients with recurrent venous thrombosis).<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

==Causes==
===Inherited===
Common types:
* [[Factor V Leiden]]: Factor V is a procoagulant which upon activation promotes the formation of thrombin. In 1994, Bertina and colleagues identified a single nucleotide polymorphism (guanine to adenine substitution in nucleotide 1691), which rendered factor V resistant to proteolytic inactivation by activated protein C (APC).<ref name="pmid8164741">{{cite journal| author=Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al.| title=Mutation in blood coagulation factor V associated with resistance to activated protein C. | journal=Nature | year= 1994 | volume= 369 | issue= 6475 | pages= 64-7 | pmid=8164741 | doi=10.1038/369064a0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8164741 }} </ref>
* [http://emedicine.medscape.com/article/209742-overview Prothrombin G20210A]: [[Prothrombin]], or factor II, is a precursor to throbmin. A single nucleotide polymorphism (guanine to adenonine substitution in in nucleotide 20210) was first identied by Poort and colleages in 1996. The mutation was associated with elevated prothrombin, thought to be due to increased translation efficiency, and an increased risk of thrombosis.<ref name="pmid8916933">{{cite journal| author=Poort SR, Rosendaal FR, Reitsma PH, Bertina RM| title=A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. | journal=Blood | year= 1996 | volume= 88 | issue= 10 | pages= 3698-703 | pmid=8916933 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8916933 }} </ref>
* Coinheritance of multiple thrombophilias is not infrequent, and does increase the thrombotic risk in affected patients.

Rare forms:
* [[Antithrombin|Antithrombin III]] deficiency
* [[Protein C deficiency]]
* [[Protein S deficiency]]
* [[Familial_dysfibrinogenemia|Dysfibrinogenemia]]
* [[Hyperhomocysteinemia]]
* '''APC resistance''' in the abscence of factor V leiden
**[https://www.snpedia.com/index.php/Rs1800595 HR2 haplotype]
**Additional mutations in the cleavage site of factor V by APC
* Increased levels of [[Factor_VIII|factor VIII]], [[Factor_IX|factor IX]], [[Factor_XI|factor XI]], or [[fibrinogen]]

===Acquired and Mixed/Unknown===
* Refer to [[Thrombophilia_classification|thrombophilia classification]]

==Causes of Thrombophilia by Organ System==

{|style="width:75%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | • [[Cerebral vein thrombosis]] • [[Acute myocardial infarction]] • [[Deep vein thrombophlebitis]] • [[Portal vein thrombosis]] • [[Pelvic thrombophlebitis]]
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| • [[Asparaginase]] • [[bevacizumab]] • [[combined oral contraceptive pill]] • [[certolizumab pegol]] • [[Ccproterone]] • [[diethylstilboestrol]] • [[drospirenone]] • [[eltrombopag]] • [[erythropoietin]] • [[ethinylestradiol]] • [[fosfestrol]] • [[granulocyte-macrophage colony stimulating factor]] • [[heparin]] • [[hormone replacement therapy]] • [[lenalidomide]] • [[peginesatide]] • [[polyestradiol]] • [[raloxifene]] • [[strontium ranelate]] • [[tamoxifen]] • [[tobacco smoking]] • [[tranexamic acid]] • [[vorinostat]]
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| • [[Hyperosmolar non-ketotic diabetic coma]]
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| • Acute [[pancreatitis]] • [[Portal hypertension]]
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[Congenital Dysfibrinogenemia]] • [[Factor II mutation]] • [[Hereditary thrombophlebitis]] • [[Antithrombin III deficiency]] • [[Factor V Leiden mutation]] • [[Protein C deficiency]] • [[Protein S deficiency]] • [[Klippel-Trenaunay syndrome]] • [[Klinefelter syndrome]] • [[Sickle cell disease]] • [[Carbohydrate-deficient glycoprotein syndrome type 1b]] • [[Factor XII deficiency]] • [[Haemoglobin SC disease]] • [[Hyperprothrombinemia 20210G-A]] • [[Plasminogen deficiency]] • [[Activated protein C resistance]] • [[CD59 antigen deficiency]] • [[Cystathionine beta-synthase deficiency]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| • [[Polycythemia vera]] • [[Essential thrombocythemia]] • [[Myeloproliferative disease]] • [[Hyperviscosity]] syndrome • [[Paroxysmal Nocturnal Hemoglobinuria]] • [[Thrombocytosis]] • Raised homocysteine levels
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| • Surgical complication
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| • [[Intraperitoneal abscess]] • [[Acute peritonitis]] • [[Visceral abscess]] • [[Diverticulitis]] • [[Intravenous catheter infection]]
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| • Orthopedic surgeries • Abdominal surgery
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| • [[Cystathionuria]] • [[Homocystinuria]] • [[Methyltetrahydrofolate reductase deficiency]] • [[Metabolic Syndrome]] • [[Insulin resistance]] • [[Folic acid deficiency]] • [[Obesity]]
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| • [[Pregnancy]] • [[Puerperium period]] • [[Ovarian hyperstimulation syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| • [[Malignancy]] • [[Peritoneal metastasis]] • [[Adenocarcinoma of cecum]] • [[Adenocarcinoma of colon]] • Occult malignancy • [[Leukemia]] • [[Pancreatic cancer]] • [[Glucagonoma]]
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"| • [[Chronic renal failure]] • [[Paroxysmal Nocturnal Hemoglobinuria]] • [[Nephrotic syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"| • [[Antiphospholipid Syndrome]] • [[Circulating anticoagulant]] • [[Heparin induced thrombocytopenia]] • [[Inflammatory bowel disease]] • [[Crohn's disease]]• [[Behcet disease]] • [[Hughes-Stovin syndrome]] • [[Polyarteritis Nodosa]] • [[SLE]]
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| • [[Trauma]] • [[Abdominal trauma]]
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| • [[Paraneoplastic syndrome]] • [[Hypereosinophilic syndrome]] • [[Immobility]]
|-
|}

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]

Thrombophilia medical therapy

2016-07-19T05:39:03Z

Asiri Saumya Ediriwickrema:

__NOTOC__

{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}
==Overview==
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

==Medical Therapy==
*Patients with provoked venous thrombosis from reversible risk factors should receive 3-6 months of anticoagulation<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
**Response to anticoagulation can be monitored clinically, with repeat ultrasongraphy for [[Deep_vein_thrombosis|deep vein thrombosis]] or measuring [[D-dimer]] levels after treatment
*Direct oral anticoagulants, including [[Direct_Xa_inhibitor|direct Xa inhibitors]] and [[Direct_thrombin_inhibitor|direct thrombin inhibitors]], should be used for long term treatment of most patients<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
:*Important exceptions include:
:**Pregnancy<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
:**Renal insufficiency
:**Malignancy<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
*[[Low_molecular_weight_heparin|Low molecular weight heparin]] is recommended for anticoagulation for the following acquired thrombophilias:
**'''Post-surgery prophylaxis'''<ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
***The duration of anticoagulation after surgery is variable. Most clinical trials have evaluated anticoagulation for 10-35 days
***General recommendations for thrombophrophylaxis is 7-10 days for standard risk patients and 10-35 days for higher risk patients as described in the algorithims below and for patients undergoing abdominal and pelvic surgeries for gynecologic malginancies<ref name="pmid20409525">{{cite journal| author=Muntz J| title=Duration of deep vein thrombosis prophylaxis in the surgical patient and its relation to quality issues. | journal=Am J Surg | year= 2010 | volume= 200 | issue= 3 | pages= 413-21 | pmid=20409525 | doi=10.1016/j.amjsurg.2009.05.045 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20409525 }} </ref>
**'''Pregnancy and postpartum'''<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
***Patients who develop acute thrombosis during pregnancy should be anticoagulated for the remainder of the their pregnancy and 6 weeks postpartum for a minimum of 3 months
***A similar duration of anticoagulation is recommended for patients with high risk thrombophilias as described in the algorithims below
**'''Malignancy'''<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
**Alternative agents include [[Warfarin]] and [[Fondaparinux]]

'''Treatment algorithms are presented below:'''

[[Image: Thrombophilia_Management_Thrombosis.jpg|thumb|center|500px|Management of acute thrombosis in patients with inherited thrombophilias]]

[[Image: Thrombophilia_Inherited_Management.jpg|thumb|center|500px|Management of asymptomatic patients with inherited thrombophilias]]

[[Image: Thrombophilia_Acquired_Management.jpg|thumb|center|500px|Management of patients with acquired thrombophilias]]

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]

Thrombophilia cost-effectiveness of therapy

2016-07-18T18:40:46Z

Asiri Saumya Ediriwickrema: /* Overview */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
It is important to determine which patients require [[Thrombophilia_screening|screening]] for thrombophilia, and subsequently which patients require [[Thrombophilia_medical_therapy|treatment]]. Certain [[Thrombophilia_history_and_symptoms|clinical scenarios]] may warrant [[Thrombophilia_screening|thrombophilia screening]].<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> Unnecessary thrombophilia screening can lead to increased costs<ref name="pmid24319155">{{cite journal| author=Hicks LK, Bering H, Carson KR, Kleinerman J, Kukreti V, Ma A et al.| title=The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. | journal=Hematology Am Soc Hematol Educ Program | year= 2013 | volume= 2013 | issue= | pages= 9-14 | pmid=24319155 | doi=10.1182/asheducation-2013.1.9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24319155 }} </ref>

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]

[[Category:Needs content]]

Thrombophilia secondary prevention

2016-07-18T18:39:51Z

Asiri Saumya Ediriwickrema: /* Overview */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
Secondary prevention strategies following acute thrombosis in patients with thrombophilia include [[anticoagulation]]. Refer to [[Thrombophilia_medical_therapy|medical therapy for thrombophilias]].

==Secondary Prevention==
Refer to [[Thrombophilia_medical_therapy|medical therapy for thrombophilias]].

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia overview

2016-07-18T18:38:25Z

Asiri Saumya Ediriwickrema: /* Prevention */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
'''Thrombophilia''' is a complex condition which increases the risk of [[thrombosis]] or thromboembolic disease. The predisposition to [[thrombus|clotting]], or '''thrombotic risk''', can be multi-factorial, and is due to an abnormality in [[coagulation]] described as '''hypercoagulability'''. Hypercoagulability is a component of [[Virchow's_triad|Virchow's Triad]], which by itself or in synergy with '''stasis''' or '''trauma''' can predispose to clot formation. The thrombotic risk associated with thrombophilic states is variable and depends on the underlying coagulopathy. Thrombophilias are classified as either inherited or a primary hypercoagulable state, acquired or a secondary hypercoagulable state, or mixed/unknown. [[Factor V Leiden]] and '''[[prothrombin]] gene mutations''' are the most common forms of inherited hypercoagulable states. Patients with thrombophilia can have a family history of [[thrombosis]], or present with frequent or unprovoked blood clots (primarily as [[deep vein thrombosis]] or [[pulmonary embolism]]), thrombosis at a young age, or blood clots in multiple or unusual sites.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis. Springer; 2014.</ref> [[Thrombophilia screening|Thrombophilia screening]] is controversial, but may aid in managing the initiation and duration of [[anticoagulation]] in affected patients and primary prevention in relatives.

==Historical Perspective==
Rudolf Virchow described hypercoagulability in the mid 1800s, however, it was not until 1965 that the first descriptions of inherited thrombophilia were published.<ref name="pmid7997003">{{cite journal| author=Schafer AI| title=Hypercoagulable states: molecular genetics to clinical practice. | journal=Lancet | year= 1994 | volume= 344 | issue= 8939-8940 | pages= 1739-42 | pmid=7997003 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7997003 }} </ref><ref name="pmid14347873">{{cite journal| author=EGEBERG O| title=INHERITED ANTITHROMBIN DEFICIENCY CAUSING THROMBOPHILIA. | journal=Thromb Diath Haemorrh | year= 1965 | volume= 13 | issue= | pages= 516-30 | pmid=14347873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14347873 }} </ref><ref name="pmid4956920">{{cite journal| author=Beck EA, Charache P, Jackson DP| title=A new inherited coagulation disorder caused by an abnormal fibrinogen ('fibrinogen Baltimore'). | journal=Nature | year= 1965 | volume= 208 | issue= 5006 | pages= 143-5 | pmid=4956920 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4956920 }} </ref> Later, in the 1990s, the more common mutations associated with primary hypercoagulable states were identified.<ref name="pmid8164741">{{cite journal| author=Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al.| title=Mutation in blood coagulation factor V associated with resistance to activated protein C. | journal=Nature | year= 1994 | volume= 369 | issue= 6475 | pages= 64-7 | pmid=8164741 | doi=10.1038/369064a0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8164741 }} </ref><ref name="pmid8916933">{{cite journal| author=Poort SR, Rosendaal FR, Reitsma PH, Bertina RM| title=A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. | journal=Blood | year= 1996 | volume= 88 | issue= 10 | pages= 3698-703 | pmid=8916933 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8916933 }} </ref>

==Classification==
Thrombophilias may be classified into three groups: '''inherited or primary hypercoagulable states''', '''acquired or secondary hypercoagulable states''', or '''mixed/unknown'''. Certain conditions are associated with greater thrombotic risks and both venous and arterial clots.

==Pathophysiology==
The pathogenesis of thrombophilia is multi-factorial. It is characterized by hypercoagulability, which by itself or in synergy with '''endothelial injury''' or '''stasis''' ([[Virchow's_triad|Virchow's Triad]]) can predispose to [[thrombus|clot formation]]. Multiple [[Thrombophilia_classification|genetic mutations and predisposing conditions]] have been associated with the increased risk of [[thrombosis]] due to abnormalities in the [[coagulation]] cascade.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The most common genes involved in the pathogenesis of acquired thrombophilias are [[Factor V Leiden]] and '''[[prothrombin]] gene mutations'''.

==Causes==
Thrombophilia may be caused by either [[Thrombophilia_classification|acquired, inherited, or, more commonly, a combination of both conditions]]. The most frequent forms of inherited thrombophilia are Factor V Leiden (20-50% prevalence in patients with recurrent venous thrombosis) and prothrombon G20210A (5-20% prevalence in patients with recurrent venous thrombosis).<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

==Differentiating Inherited Thrombophilia from other Diseases==
Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]. Inherited thrombophilias should be suspected in patients with the certain [[Thrombophilia_history_and_symptoms|clinical presentations]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> [[Thrombophilia screening|Screening]] for inherited thrombophilias is controversial and should be performed in the appropriate clinical context.<ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

==Epidemiology and Demographics==
Due to the multitude and complexity of inherited thrombophilias, the true [[prevalence]] is unknown, and current data may be providing an underestimate. Comparison among different epidemiologic studies becomes difficult due to variation in study design and inclusion criteria. Prevalence of common inherited thrombophilias is variable among both healthy patients and patients with recurrent [[thrombosis]]. According to epidemiologic and modeling studies obtained from certain sources, the prevalence of inherited thrombophilias was estimated to be between 0.01-7% in caucasians.<ref name="pmid26780744">{{cite journal| author=Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M et al.| title=Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 154-64 | pmid=26780744 | doi=10.1007/s11239-015-1316-1 | pmc=4715840 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780744 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> In certain studies, the prevalence of inherited thrombophilias, specifically, '''activated protein C resistance''' and '''prothrombin G20210A''', rises to approximately 10-60% in patients with documented venous thrombosis compared to less than 10% among controls.<ref name="pmid9669991">{{cite journal| author=Margaglione M, Brancaccio V, Giuliani N, D'Andrea G, Cappucci G, Iannaccone L et al.| title=Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant. | journal=Ann Intern Med | year= 1998 | volume= 129 | issue= 2 | pages= 89-93 | pmid=9669991 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9669991 }} </ref><ref name="pmid7877648">{{cite journal| author=Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP| title=Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. | journal=N Engl J Med | year= 1995 | volume= 332 | issue= 14 | pages= 912-7 | pmid=7877648 | doi=10.1056/NEJM199504063321403 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7877648 }} </ref><ref name="pmid7902898">{{cite journal| author=Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM| title=Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. | journal=Lancet | year= 1993 | volume= 342 | issue= 8886-8887 | pages= 1503-6 | pmid=7902898 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7902898 }} </ref> The incidence of inherited thrombophilia in incident venous thrombosis is approximately 150-840 per 100,000 person years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref> The incidence of inherited thrombophilia in recurrent venous thrombosis is approximately 3,500-10,500 per 100,000 person-years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

===Age===
Patients of all age groups may develop thrombophilias. Acquired thrombophilias are more commonly observed among elderly patients (age > 60) as age is a risk factor for thrombosis. Inherited thrombophilias can be seen among young patients aged <40-55 years old.

===Gender===
Epidemiologic studies have provided mixed results regarding the effect of gender on venous thrombosis. Certain groups observed increased risk of thrombosis in younger females and older males, whereas other groups found similar frequencies in both genders.<ref name="pmid12814979">{{cite journal| author=White RH| title=The epidemiology of venous thromboembolism. | journal=Circulation | year= 2003 | volume= 107 | issue= 23 Suppl 1 | pages= I4-8 | pmid=12814979 | doi=10.1161/01.CIR.0000078468.11849.66 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12814979 }} </ref> A prospective follow up study performed by Christiansen et al, revealed an age corrected hazard ratio of 2.7 of recurrent thrombosis in male patients with inherited thrombophilias compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref> In patients with inherited thrombophilias, a prospective follow up study performed by Christiansen et al revealed an age corrected hazard ratio of 2.7 for recurrent thrombosis in male patients compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref>

===Race===
The factor V leiden G1691A and prothrombin G20210A mutations are exceedingly rare in non-white populations.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

==Risk Factors==
The most common risk factors in the development of acquired thrombophlias are trauma, surgery, immobility, pregnancy, estrogen therapy, and age. The most common risk factors in the development of inherited thrombophilias are genetic mutations in factor V leiden and prothrombon G20210A.

== Natural History, Complications and Prognosis==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref> If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) is low (<0.06%) .<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref> Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref> Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref> OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref> Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

== Diagnosis ==
===Diagnostic Criteria===
The diagnosis of an inherited thrombophilia is made with specific [[Thrombophilia_laboratory_findings|laboratory tests]] for each inherited condition.

=== Symptoms ===
Common symptoms of thrombophilias may include symptoms of [[Deep venous thrombosis]], [[Pulmonary embolus]], and superficial venous thrombosis.

=== Physical Examination ===
Physical examination of patients with thrombophilia is usually remarkable for signs of [[Deep_vein_thrombosis_physical_examination|deep venous thrombosis]], [[Pulmonary_embolism_physical_examination|pulmonary thrombosis]], [[Renal_vein_thrombosis|renal vein thrombosis]], [[Cerebral_venous_sinus_thrombosis_physical_examination|cerebral vein thrombosis]], [[Superficial_vein_thrombosis|superficial vein thrombosis]], arterial thrombosis, [[Portal_hypertension_physical_examination|portal hypertension]] which can be sign of [https://en.wikipedia.org/wiki/Portal_vein_thrombosis| portal vein thrombosis], [[Warfarin_necrosis|warfarin skin necrosis]], or [https://en.wikipedia.org/wiki/Livedo_reticularis livedo reticularis].<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

=== Screening ===
According to the American Society of Hematology, screening for inherited thrombophilias in adult patients with venous [[thrombosis]] in the setting of major transient risk factors which include surgery, trauma, or prolonged immobility is not recommended.<ref name="pmid24319155">{{cite journal| author=Hicks LK, Bering H, Carson KR, Kleinerman J, Kukreti V, Ma A et al.| title=The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. | journal=Hematology Am Soc Hematol Educ Program | year= 2013 | volume= 2013 | issue= | pages= 9-14 | pmid=24319155 | doi=10.1182/asheducation-2013.1.9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24319155 }} </ref> However, given the [[Thrombophilia_natural_history,_complications_and_prognosis|associated risks]] for recurrent thrombosis, patients who have significant risk factors including a positive family history or concurrent treatment with hormonal therapies should seek expert consultation.

=== Laboratory Findings ===
Laboratory findings consistent with the diagnosis of inherited thrombophilias include specific [[Thrombophilia_laboratory_findings|laboratory findings]] associated with each inherited thrombophilia.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

===Imaging Findings===
[[Ultrasound|Ultrasongraphy]], [https://en.wikipedia.org/wiki/Computed_tomography_angiography| computed tomography angiography (CTA or CT Angiography)], [https://en.wikipedia.org/wiki/Magnetic_resonance_angiography| magnetic resonance angiography (MRA or MR Angiography)] and [[Angiogram|projectional angiography]] may be diagnostic of acute thrombosis, which is associated with the diagnosis of thrombophilia.

== Treatment ==
=== Medical Therapy ===
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

=== Surgery ===
Surgery is not required for treatment for thrombophilia. [[IVC_filter|IVC filter]] placement may be indicated if the patient has contraindications to or complications from [[anticoagulation]], recurrent thrombosis on anticoagulation, or failure to acheive therapeutic anticoagulation levels.<ref> Inferior Vena Cava Filters. Medscape (2015). URL Accessed on July 17, 2016</ref>

=== Prevention ===
[[Thrombophilia_medical_therapy|Prophylaxis]] with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|certain scenarios]]. Once diagnosed and successfully treated, patients with thrombophilia are followed-up routinely to monitor anticoagulation and clinically if thrombosis recurrs

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Hematology]]
[[Category:Primary care]]

Thrombophilia primary prevention

2016-07-18T18:38:13Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Thrombophilia_medical_therapy|Prophylaxis]] with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|certain scenarios]].

==Primary Prevention==
[[Thrombophilia_medical_therapy|Prophylaxis]] with [[anticoagulation]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|certain scenarios]].

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia primary prevention

2016-07-18T18:37:05Z

Asiri Saumya Ediriwickrema: udpate

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Thrombophilia_medical_therapy|Prophylaxis]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|certain scenarios]].

==Primary Prevention==
[[Thrombophilia_medical_therapy|Prophylaxis]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|certain scenarios]].

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia primary prevention

2016-07-18T18:36:25Z

Asiri Saumya Ediriwickrema: /* Overview */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Thrombophilia_medical_therapy|Prophylaxis]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|certain scenarios]].

==Primary Prevention==
Refer to [[Thrombophilia_medical_therapy|medical therapy for thrombophilias]].

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia overview

2016-07-18T18:35:43Z

Asiri Saumya Ediriwickrema: /* Prevention */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
'''Thrombophilia''' is a complex condition which increases the risk of [[thrombosis]] or thromboembolic disease. The predisposition to [[thrombus|clotting]], or '''thrombotic risk''', can be multi-factorial, and is due to an abnormality in [[coagulation]] described as '''hypercoagulability'''. Hypercoagulability is a component of [[Virchow's_triad|Virchow's Triad]], which by itself or in synergy with '''stasis''' or '''trauma''' can predispose to clot formation. The thrombotic risk associated with thrombophilic states is variable and depends on the underlying coagulopathy. Thrombophilias are classified as either inherited or a primary hypercoagulable state, acquired or a secondary hypercoagulable state, or mixed/unknown. [[Factor V Leiden]] and '''[[prothrombin]] gene mutations''' are the most common forms of inherited hypercoagulable states. Patients with thrombophilia can have a family history of [[thrombosis]], or present with frequent or unprovoked blood clots (primarily as [[deep vein thrombosis]] or [[pulmonary embolism]]), thrombosis at a young age, or blood clots in multiple or unusual sites.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis. Springer; 2014.</ref> [[Thrombophilia screening|Thrombophilia screening]] is controversial, but may aid in managing the initiation and duration of [[anticoagulation]] in affected patients and primary prevention in relatives.

==Historical Perspective==
Rudolf Virchow described hypercoagulability in the mid 1800s, however, it was not until 1965 that the first descriptions of inherited thrombophilia were published.<ref name="pmid7997003">{{cite journal| author=Schafer AI| title=Hypercoagulable states: molecular genetics to clinical practice. | journal=Lancet | year= 1994 | volume= 344 | issue= 8939-8940 | pages= 1739-42 | pmid=7997003 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7997003 }} </ref><ref name="pmid14347873">{{cite journal| author=EGEBERG O| title=INHERITED ANTITHROMBIN DEFICIENCY CAUSING THROMBOPHILIA. | journal=Thromb Diath Haemorrh | year= 1965 | volume= 13 | issue= | pages= 516-30 | pmid=14347873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14347873 }} </ref><ref name="pmid4956920">{{cite journal| author=Beck EA, Charache P, Jackson DP| title=A new inherited coagulation disorder caused by an abnormal fibrinogen ('fibrinogen Baltimore'). | journal=Nature | year= 1965 | volume= 208 | issue= 5006 | pages= 143-5 | pmid=4956920 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4956920 }} </ref> Later, in the 1990s, the more common mutations associated with primary hypercoagulable states were identified.<ref name="pmid8164741">{{cite journal| author=Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al.| title=Mutation in blood coagulation factor V associated with resistance to activated protein C. | journal=Nature | year= 1994 | volume= 369 | issue= 6475 | pages= 64-7 | pmid=8164741 | doi=10.1038/369064a0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8164741 }} </ref><ref name="pmid8916933">{{cite journal| author=Poort SR, Rosendaal FR, Reitsma PH, Bertina RM| title=A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. | journal=Blood | year= 1996 | volume= 88 | issue= 10 | pages= 3698-703 | pmid=8916933 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8916933 }} </ref>

==Classification==
Thrombophilias may be classified into three groups: '''inherited or primary hypercoagulable states''', '''acquired or secondary hypercoagulable states''', or '''mixed/unknown'''. Certain conditions are associated with greater thrombotic risks and both venous and arterial clots.

==Pathophysiology==
The pathogenesis of thrombophilia is multi-factorial. It is characterized by hypercoagulability, which by itself or in synergy with '''endothelial injury''' or '''stasis''' ([[Virchow's_triad|Virchow's Triad]]) can predispose to [[thrombus|clot formation]]. Multiple [[Thrombophilia_classification|genetic mutations and predisposing conditions]] have been associated with the increased risk of [[thrombosis]] due to abnormalities in the [[coagulation]] cascade.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The most common genes involved in the pathogenesis of acquired thrombophilias are [[Factor V Leiden]] and '''[[prothrombin]] gene mutations'''.

==Causes==
Thrombophilia may be caused by either [[Thrombophilia_classification|acquired, inherited, or, more commonly, a combination of both conditions]]. The most frequent forms of inherited thrombophilia are Factor V Leiden (20-50% prevalence in patients with recurrent venous thrombosis) and prothrombon G20210A (5-20% prevalence in patients with recurrent venous thrombosis).<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

==Differentiating Inherited Thrombophilia from other Diseases==
Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]. Inherited thrombophilias should be suspected in patients with the certain [[Thrombophilia_history_and_symptoms|clinical presentations]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> [[Thrombophilia screening|Screening]] for inherited thrombophilias is controversial and should be performed in the appropriate clinical context.<ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

==Epidemiology and Demographics==
Due to the multitude and complexity of inherited thrombophilias, the true [[prevalence]] is unknown, and current data may be providing an underestimate. Comparison among different epidemiologic studies becomes difficult due to variation in study design and inclusion criteria. Prevalence of common inherited thrombophilias is variable among both healthy patients and patients with recurrent [[thrombosis]]. According to epidemiologic and modeling studies obtained from certain sources, the prevalence of inherited thrombophilias was estimated to be between 0.01-7% in caucasians.<ref name="pmid26780744">{{cite journal| author=Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M et al.| title=Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 154-64 | pmid=26780744 | doi=10.1007/s11239-015-1316-1 | pmc=4715840 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780744 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> In certain studies, the prevalence of inherited thrombophilias, specifically, '''activated protein C resistance''' and '''prothrombin G20210A''', rises to approximately 10-60% in patients with documented venous thrombosis compared to less than 10% among controls.<ref name="pmid9669991">{{cite journal| author=Margaglione M, Brancaccio V, Giuliani N, D'Andrea G, Cappucci G, Iannaccone L et al.| title=Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant. | journal=Ann Intern Med | year= 1998 | volume= 129 | issue= 2 | pages= 89-93 | pmid=9669991 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9669991 }} </ref><ref name="pmid7877648">{{cite journal| author=Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP| title=Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. | journal=N Engl J Med | year= 1995 | volume= 332 | issue= 14 | pages= 912-7 | pmid=7877648 | doi=10.1056/NEJM199504063321403 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7877648 }} </ref><ref name="pmid7902898">{{cite journal| author=Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM| title=Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. | journal=Lancet | year= 1993 | volume= 342 | issue= 8886-8887 | pages= 1503-6 | pmid=7902898 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7902898 }} </ref> The incidence of inherited thrombophilia in incident venous thrombosis is approximately 150-840 per 100,000 person years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref> The incidence of inherited thrombophilia in recurrent venous thrombosis is approximately 3,500-10,500 per 100,000 person-years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

===Age===
Patients of all age groups may develop thrombophilias. Acquired thrombophilias are more commonly observed among elderly patients (age > 60) as age is a risk factor for thrombosis. Inherited thrombophilias can be seen among young patients aged <40-55 years old.

===Gender===
Epidemiologic studies have provided mixed results regarding the effect of gender on venous thrombosis. Certain groups observed increased risk of thrombosis in younger females and older males, whereas other groups found similar frequencies in both genders.<ref name="pmid12814979">{{cite journal| author=White RH| title=The epidemiology of venous thromboembolism. | journal=Circulation | year= 2003 | volume= 107 | issue= 23 Suppl 1 | pages= I4-8 | pmid=12814979 | doi=10.1161/01.CIR.0000078468.11849.66 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12814979 }} </ref> A prospective follow up study performed by Christiansen et al, revealed an age corrected hazard ratio of 2.7 of recurrent thrombosis in male patients with inherited thrombophilias compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref> In patients with inherited thrombophilias, a prospective follow up study performed by Christiansen et al revealed an age corrected hazard ratio of 2.7 for recurrent thrombosis in male patients compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref>

===Race===
The factor V leiden G1691A and prothrombin G20210A mutations are exceedingly rare in non-white populations.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

==Risk Factors==
The most common risk factors in the development of acquired thrombophlias are trauma, surgery, immobility, pregnancy, estrogen therapy, and age. The most common risk factors in the development of inherited thrombophilias are genetic mutations in factor V leiden and prothrombon G20210A.

== Natural History, Complications and Prognosis==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref> If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) is low (<0.06%) .<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref> Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref> Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref> OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref> Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

== Diagnosis ==
===Diagnostic Criteria===
The diagnosis of an inherited thrombophilia is made with specific [[Thrombophilia_laboratory_findings|laboratory tests]] for each inherited condition.

=== Symptoms ===
Common symptoms of thrombophilias may include symptoms of [[Deep venous thrombosis]], [[Pulmonary embolus]], and superficial venous thrombosis.

=== Physical Examination ===
Physical examination of patients with thrombophilia is usually remarkable for signs of [[Deep_vein_thrombosis_physical_examination|deep venous thrombosis]], [[Pulmonary_embolism_physical_examination|pulmonary thrombosis]], [[Renal_vein_thrombosis|renal vein thrombosis]], [[Cerebral_venous_sinus_thrombosis_physical_examination|cerebral vein thrombosis]], [[Superficial_vein_thrombosis|superficial vein thrombosis]], arterial thrombosis, [[Portal_hypertension_physical_examination|portal hypertension]] which can be sign of [https://en.wikipedia.org/wiki/Portal_vein_thrombosis| portal vein thrombosis], [[Warfarin_necrosis|warfarin skin necrosis]], or [https://en.wikipedia.org/wiki/Livedo_reticularis livedo reticularis].<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

=== Screening ===
According to the American Society of Hematology, screening for inherited thrombophilias in adult patients with venous [[thrombosis]] in the setting of major transient risk factors which include surgery, trauma, or prolonged immobility is not recommended.<ref name="pmid24319155">{{cite journal| author=Hicks LK, Bering H, Carson KR, Kleinerman J, Kukreti V, Ma A et al.| title=The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. | journal=Hematology Am Soc Hematol Educ Program | year= 2013 | volume= 2013 | issue= | pages= 9-14 | pmid=24319155 | doi=10.1182/asheducation-2013.1.9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24319155 }} </ref> However, given the [[Thrombophilia_natural_history,_complications_and_prognosis|associated risks]] for recurrent thrombosis, patients who have significant risk factors including a positive family history or concurrent treatment with hormonal therapies should seek expert consultation.

=== Laboratory Findings ===
Laboratory findings consistent with the diagnosis of inherited thrombophilias include specific [[Thrombophilia_laboratory_findings|laboratory findings]] associated with each inherited thrombophilia.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

===Imaging Findings===
[[Ultrasound|Ultrasongraphy]], [https://en.wikipedia.org/wiki/Computed_tomography_angiography| computed tomography angiography (CTA or CT Angiography)], [https://en.wikipedia.org/wiki/Magnetic_resonance_angiography| magnetic resonance angiography (MRA or MR Angiography)] and [[Angiogram|projectional angiography]] may be diagnostic of acute thrombosis, which is associated with the diagnosis of thrombophilia.

== Treatment ==
=== Medical Therapy ===
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

=== Surgery ===
Surgery is not required for treatment for thrombophilia. [[IVC_filter|IVC filter]] placement may be indicated if the patient has contraindications to or complications from [[anticoagulation]], recurrent thrombosis on anticoagulation, or failure to acheive therapeutic anticoagulation levels.<ref> Inferior Vena Cava Filters. Medscape (2015). URL Accessed on July 17, 2016</ref>

=== Prevention ===
[[Thrombophilia_medical_therapy|Prophylaxis]] may be recommended for primary prevention of acute thrombosis in [[Thrombophilia_medical_therapy|certain scenarios]]. Once diagnosed and successfully treated, patients with thrombophilia are followed-up routinely to monitor anticoagulation and clinically if thrombosis recurrs

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Hematology]]
[[Category:Primary care]]

Thrombophilia surgery

2016-07-18T18:33:11Z

Asiri Saumya Ediriwickrema: update

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
Surgery is not required for treatment for thrombophilia. [[IVC_filter|IVC filter]] placement may be indicated if the patient has contraindications to or complications from [[anticoagulation]], recurrent thrombosis on anticoagulation, or failure to acheive therapeutic anticoagulation levels.<ref> Inferior Vena Cava Filters. Medscape (2015). URL Accessed on July 17, 2016</ref>

==Surgery==
*Surgery is not required for treatment for thrombophilia
*[[IVC_filter|IVC filter]] placement may be indicated in certain scenarios:
**Contraindications to or complications from [[anticoagulation]]
**Recurrent thrombosis on anticoagulation, or failure to acheive therapeutic anticoagulation levels

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia overview

2016-07-18T18:32:54Z

Asiri Saumya Ediriwickrema: update

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
'''Thrombophilia''' is a complex condition which increases the risk of [[thrombosis]] or thromboembolic disease. The predisposition to [[thrombus|clotting]], or '''thrombotic risk''', can be multi-factorial, and is due to an abnormality in [[coagulation]] described as '''hypercoagulability'''. Hypercoagulability is a component of [[Virchow's_triad|Virchow's Triad]], which by itself or in synergy with '''stasis''' or '''trauma''' can predispose to clot formation. The thrombotic risk associated with thrombophilic states is variable and depends on the underlying coagulopathy. Thrombophilias are classified as either inherited or a primary hypercoagulable state, acquired or a secondary hypercoagulable state, or mixed/unknown. [[Factor V Leiden]] and '''[[prothrombin]] gene mutations''' are the most common forms of inherited hypercoagulable states. Patients with thrombophilia can have a family history of [[thrombosis]], or present with frequent or unprovoked blood clots (primarily as [[deep vein thrombosis]] or [[pulmonary embolism]]), thrombosis at a young age, or blood clots in multiple or unusual sites.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis. Springer; 2014.</ref> [[Thrombophilia screening|Thrombophilia screening]] is controversial, but may aid in managing the initiation and duration of [[anticoagulation]] in affected patients and primary prevention in relatives.

==Historical Perspective==
Rudolf Virchow described hypercoagulability in the mid 1800s, however, it was not until 1965 that the first descriptions of inherited thrombophilia were published.<ref name="pmid7997003">{{cite journal| author=Schafer AI| title=Hypercoagulable states: molecular genetics to clinical practice. | journal=Lancet | year= 1994 | volume= 344 | issue= 8939-8940 | pages= 1739-42 | pmid=7997003 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7997003 }} </ref><ref name="pmid14347873">{{cite journal| author=EGEBERG O| title=INHERITED ANTITHROMBIN DEFICIENCY CAUSING THROMBOPHILIA. | journal=Thromb Diath Haemorrh | year= 1965 | volume= 13 | issue= | pages= 516-30 | pmid=14347873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14347873 }} </ref><ref name="pmid4956920">{{cite journal| author=Beck EA, Charache P, Jackson DP| title=A new inherited coagulation disorder caused by an abnormal fibrinogen ('fibrinogen Baltimore'). | journal=Nature | year= 1965 | volume= 208 | issue= 5006 | pages= 143-5 | pmid=4956920 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4956920 }} </ref> Later, in the 1990s, the more common mutations associated with primary hypercoagulable states were identified.<ref name="pmid8164741">{{cite journal| author=Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al.| title=Mutation in blood coagulation factor V associated with resistance to activated protein C. | journal=Nature | year= 1994 | volume= 369 | issue= 6475 | pages= 64-7 | pmid=8164741 | doi=10.1038/369064a0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8164741 }} </ref><ref name="pmid8916933">{{cite journal| author=Poort SR, Rosendaal FR, Reitsma PH, Bertina RM| title=A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. | journal=Blood | year= 1996 | volume= 88 | issue= 10 | pages= 3698-703 | pmid=8916933 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8916933 }} </ref>

==Classification==
Thrombophilias may be classified into three groups: '''inherited or primary hypercoagulable states''', '''acquired or secondary hypercoagulable states''', or '''mixed/unknown'''. Certain conditions are associated with greater thrombotic risks and both venous and arterial clots.

==Pathophysiology==
The pathogenesis of thrombophilia is multi-factorial. It is characterized by hypercoagulability, which by itself or in synergy with '''endothelial injury''' or '''stasis''' ([[Virchow's_triad|Virchow's Triad]]) can predispose to [[thrombus|clot formation]]. Multiple [[Thrombophilia_classification|genetic mutations and predisposing conditions]] have been associated with the increased risk of [[thrombosis]] due to abnormalities in the [[coagulation]] cascade.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The most common genes involved in the pathogenesis of acquired thrombophilias are [[Factor V Leiden]] and '''[[prothrombin]] gene mutations'''.

==Causes==
Thrombophilia may be caused by either [[Thrombophilia_classification|acquired, inherited, or, more commonly, a combination of both conditions]]. The most frequent forms of inherited thrombophilia are Factor V Leiden (20-50% prevalence in patients with recurrent venous thrombosis) and prothrombon G20210A (5-20% prevalence in patients with recurrent venous thrombosis).<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

==Differentiating Inherited Thrombophilia from other Diseases==
Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]. Inherited thrombophilias should be suspected in patients with the certain [[Thrombophilia_history_and_symptoms|clinical presentations]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> [[Thrombophilia screening|Screening]] for inherited thrombophilias is controversial and should be performed in the appropriate clinical context.<ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

==Epidemiology and Demographics==
Due to the multitude and complexity of inherited thrombophilias, the true [[prevalence]] is unknown, and current data may be providing an underestimate. Comparison among different epidemiologic studies becomes difficult due to variation in study design and inclusion criteria. Prevalence of common inherited thrombophilias is variable among both healthy patients and patients with recurrent [[thrombosis]]. According to epidemiologic and modeling studies obtained from certain sources, the prevalence of inherited thrombophilias was estimated to be between 0.01-7% in caucasians.<ref name="pmid26780744">{{cite journal| author=Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M et al.| title=Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 154-64 | pmid=26780744 | doi=10.1007/s11239-015-1316-1 | pmc=4715840 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780744 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> In certain studies, the prevalence of inherited thrombophilias, specifically, '''activated protein C resistance''' and '''prothrombin G20210A''', rises to approximately 10-60% in patients with documented venous thrombosis compared to less than 10% among controls.<ref name="pmid9669991">{{cite journal| author=Margaglione M, Brancaccio V, Giuliani N, D'Andrea G, Cappucci G, Iannaccone L et al.| title=Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant. | journal=Ann Intern Med | year= 1998 | volume= 129 | issue= 2 | pages= 89-93 | pmid=9669991 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9669991 }} </ref><ref name="pmid7877648">{{cite journal| author=Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP| title=Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. | journal=N Engl J Med | year= 1995 | volume= 332 | issue= 14 | pages= 912-7 | pmid=7877648 | doi=10.1056/NEJM199504063321403 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7877648 }} </ref><ref name="pmid7902898">{{cite journal| author=Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM| title=Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. | journal=Lancet | year= 1993 | volume= 342 | issue= 8886-8887 | pages= 1503-6 | pmid=7902898 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7902898 }} </ref> The incidence of inherited thrombophilia in incident venous thrombosis is approximately 150-840 per 100,000 person years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref> The incidence of inherited thrombophilia in recurrent venous thrombosis is approximately 3,500-10,500 per 100,000 person-years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

===Age===
Patients of all age groups may develop thrombophilias. Acquired thrombophilias are more commonly observed among elderly patients (age > 60) as age is a risk factor for thrombosis. Inherited thrombophilias can be seen among young patients aged <40-55 years old.

===Gender===
Epidemiologic studies have provided mixed results regarding the effect of gender on venous thrombosis. Certain groups observed increased risk of thrombosis in younger females and older males, whereas other groups found similar frequencies in both genders.<ref name="pmid12814979">{{cite journal| author=White RH| title=The epidemiology of venous thromboembolism. | journal=Circulation | year= 2003 | volume= 107 | issue= 23 Suppl 1 | pages= I4-8 | pmid=12814979 | doi=10.1161/01.CIR.0000078468.11849.66 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12814979 }} </ref> A prospective follow up study performed by Christiansen et al, revealed an age corrected hazard ratio of 2.7 of recurrent thrombosis in male patients with inherited thrombophilias compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref> In patients with inherited thrombophilias, a prospective follow up study performed by Christiansen et al revealed an age corrected hazard ratio of 2.7 for recurrent thrombosis in male patients compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref>

===Race===
The factor V leiden G1691A and prothrombin G20210A mutations are exceedingly rare in non-white populations.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

==Risk Factors==
The most common risk factors in the development of acquired thrombophlias are trauma, surgery, immobility, pregnancy, estrogen therapy, and age. The most common risk factors in the development of inherited thrombophilias are genetic mutations in factor V leiden and prothrombon G20210A.

== Natural History, Complications and Prognosis==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref> If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) is low (<0.06%) .<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref> Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref> Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref> OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref> Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

== Diagnosis ==
===Diagnostic Criteria===
The diagnosis of an inherited thrombophilia is made with specific [[Thrombophilia_laboratory_findings|laboratory tests]] for each inherited condition.

=== Symptoms ===
Common symptoms of thrombophilias may include symptoms of [[Deep venous thrombosis]], [[Pulmonary embolus]], and superficial venous thrombosis.

=== Physical Examination ===
Physical examination of patients with thrombophilia is usually remarkable for signs of [[Deep_vein_thrombosis_physical_examination|deep venous thrombosis]], [[Pulmonary_embolism_physical_examination|pulmonary thrombosis]], [[Renal_vein_thrombosis|renal vein thrombosis]], [[Cerebral_venous_sinus_thrombosis_physical_examination|cerebral vein thrombosis]], [[Superficial_vein_thrombosis|superficial vein thrombosis]], arterial thrombosis, [[Portal_hypertension_physical_examination|portal hypertension]] which can be sign of [https://en.wikipedia.org/wiki/Portal_vein_thrombosis| portal vein thrombosis], [[Warfarin_necrosis|warfarin skin necrosis]], or [https://en.wikipedia.org/wiki/Livedo_reticularis livedo reticularis].<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

=== Screening ===
According to the American Society of Hematology, screening for inherited thrombophilias in adult patients with venous [[thrombosis]] in the setting of major transient risk factors which include surgery, trauma, or prolonged immobility is not recommended.<ref name="pmid24319155">{{cite journal| author=Hicks LK, Bering H, Carson KR, Kleinerman J, Kukreti V, Ma A et al.| title=The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. | journal=Hematology Am Soc Hematol Educ Program | year= 2013 | volume= 2013 | issue= | pages= 9-14 | pmid=24319155 | doi=10.1182/asheducation-2013.1.9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24319155 }} </ref> However, given the [[Thrombophilia_natural_history,_complications_and_prognosis|associated risks]] for recurrent thrombosis, patients who have significant risk factors including a positive family history or concurrent treatment with hormonal therapies should seek expert consultation.

=== Laboratory Findings ===
Laboratory findings consistent with the diagnosis of inherited thrombophilias include specific [[Thrombophilia_laboratory_findings|laboratory findings]] associated with each inherited thrombophilia.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

===Imaging Findings===
[[Ultrasound|Ultrasongraphy]], [https://en.wikipedia.org/wiki/Computed_tomography_angiography| computed tomography angiography (CTA or CT Angiography)], [https://en.wikipedia.org/wiki/Magnetic_resonance_angiography| magnetic resonance angiography (MRA or MR Angiography)] and [[Angiogram|projectional angiography]] may be diagnostic of acute thrombosis, which is associated with the diagnosis of thrombophilia.

== Treatment ==
=== Medical Therapy ===
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

=== Surgery ===
Surgery is not required for treatment for thrombophilia. [[IVC_filter|IVC filter]] placement may be indicated if the patient has contraindications to or complications from [[anticoagulation]], recurrent thrombosis on anticoagulation, or failure to acheive therapeutic anticoagulation levels.<ref> Inferior Vena Cava Filters. Medscape (2015). URL Accessed on July 17, 2016</ref>

=== Prevention ===
*[[Thrombophilia_medical_therapy|Prophylaxis]] may be indicated for thrombophilia in certain scenarios
*Once diagnosed and successfully treated, patients with thrombophilia are followed-up routinely to monitor anticoagulation and clinically if thrombosis recurrs

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Hematology]]
[[Category:Primary care]]

Thrombophilia medical therapy

2016-07-18T18:28:19Z

Asiri Saumya Ediriwickrema: /* Overview */

__NOTOC__

{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}
==Overview==
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

==Medical Therapy==
*Patients with provoked venous thrombosis from reversible risk factors should receive 3-6 months of anticoagulation<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
**Response to anticoagulation can be monitored clinically, with repeat ultrasongraphy for [[Deep_vein_thrombosis|deep vein thrombosis]] or measuring [[D-dimer]] levels after treatment
*Direct oral anticoagulants, including [[Direct_Xa_inhibitor|direct Xa inhibitors]] and [[Direct_thrombin_inhibitor|direct thrombin inhibitors]], should be used for long term treatment of most patients<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref>
:*Important exceptions include:
:**Pregnancy<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
:**Renal insufficiency
:**Malignancy<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
*[[Low_molecular_weight_heparin|Low molecular weight heparin]] is recommended for anticoagulation for the following acquired thrombophilias:
**'''Post-surgery prophylaxis'''<ref name="pmid22315265">{{cite journal| author=Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S et al.| title=Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e278S-325S | pmid=22315265 | doi=10.1378/chest.11-2404 | pmc=3278063 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315265 }} </ref><ref name="pmid11919306">{{cite journal| author=Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al.| title=Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. | journal=N Engl J Med | year= 2002 | volume= 346 | issue= 13 | pages= 975-80 | pmid=11919306 | doi=10.1056/NEJMoa012385 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11919306 }} </ref><ref name="pmid15598646">{{cite journal| author=Agnelli G| title=Prevention of venous thromboembolism in surgical patients. | journal=Circulation | year= 2004 | volume= 110 | issue= 24 Suppl 1 | pages= IV4-12 | pmid=15598646 | doi=10.1161/01.CIR.0000150639.98514.6c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15598646 }} </ref>
***The duration of anticoagulation after surgery is variable. Most clinical trials have evaluated anticoagulation for 10-35 days
***General recommendations for thrombophrophylaxis is 7-10 days for standard risk patients and 10-35 days for higher risk patients as described in the algorithims below and for patients undergoing abdominal and pelvic surgeries for gynecologic malginancies<ref name="pmid20409525">{{cite journal| author=Muntz J| title=Duration of deep vein thrombosis prophylaxis in the surgical patient and its relation to quality issues. | journal=Am J Surg | year= 2010 | volume= 200 | issue= 3 | pages= 413-21 | pmid=20409525 | doi=10.1016/j.amjsurg.2009.05.045 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20409525 }} </ref>
**'''Pregnancy and postpartum'''<ref name="pmid22315276">{{cite journal| author=Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO et al.| title=VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e691S-736S | pmid=22315276 | doi=10.1378/chest.11-2300 | pmc=3278054 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315276 }} </ref>
***Patients who develop acute thrombosis during pregnancy should be anticoagulated for the remainder of the their pregnancy and 6 weeks postpartum for a minimum of 3 months
***A similar duration of anticoagulation is recommended for patients with high risk thrombophilias as described in the algorithims below
**'''Malignancy'''<ref name="pmid12853587">{{cite journal| author=Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al.| title=Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 2 | pages= 146-53 | pmid=12853587 | doi=10.1056/NEJMoa025313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12853587 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14711281 Review in: ACP J Club. 2004 Jan-Feb;140(1):10] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14599373 Review in: J Fam Pract. 2003 Nov;52(11):843-4] </ref>
**Alternative agents include [[Warfarin]] and [[Fondaparinux]]

'''Treatment algorithms are presented below:'''

[[Image: Thrombophilia_Management_Thrombosis.jpg|thumb|center|700px|Management of acute thrombosis in patients with inherited thrombophilias]]

[[Image: Thrombophilia_Inherited_Management.jpg|thumb|center|500px|Management of asymptomatic patients with inherited thrombophilias]]

[[Image: Thrombophilia_Acquired_Management.jpg|thumb|center|500px|Management of patients with acquired thrombophilias]]

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Hematology]]

Thrombophilia overview

2016-07-18T18:27:53Z

Asiri Saumya Ediriwickrema: /* Medical Therapy */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
'''Thrombophilia''' is a complex condition which increases the risk of [[thrombosis]] or thromboembolic disease. The predisposition to [[thrombus|clotting]], or '''thrombotic risk''', can be multi-factorial, and is due to an abnormality in [[coagulation]] described as '''hypercoagulability'''. Hypercoagulability is a component of [[Virchow's_triad|Virchow's Triad]], which by itself or in synergy with '''stasis''' or '''trauma''' can predispose to clot formation. The thrombotic risk associated with thrombophilic states is variable and depends on the underlying coagulopathy. Thrombophilias are classified as either inherited or a primary hypercoagulable state, acquired or a secondary hypercoagulable state, or mixed/unknown. [[Factor V Leiden]] and '''[[prothrombin]] gene mutations''' are the most common forms of inherited hypercoagulable states. Patients with thrombophilia can have a family history of [[thrombosis]], or present with frequent or unprovoked blood clots (primarily as [[deep vein thrombosis]] or [[pulmonary embolism]]), thrombosis at a young age, or blood clots in multiple or unusual sites.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis. Springer; 2014.</ref> [[Thrombophilia screening|Thrombophilia screening]] is controversial, but may aid in managing the initiation and duration of [[anticoagulation]] in affected patients and primary prevention in relatives.

==Historical Perspective==
Rudolf Virchow described hypercoagulability in the mid 1800s, however, it was not until 1965 that the first descriptions of inherited thrombophilia were published.<ref name="pmid7997003">{{cite journal| author=Schafer AI| title=Hypercoagulable states: molecular genetics to clinical practice. | journal=Lancet | year= 1994 | volume= 344 | issue= 8939-8940 | pages= 1739-42 | pmid=7997003 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7997003 }} </ref><ref name="pmid14347873">{{cite journal| author=EGEBERG O| title=INHERITED ANTITHROMBIN DEFICIENCY CAUSING THROMBOPHILIA. | journal=Thromb Diath Haemorrh | year= 1965 | volume= 13 | issue= | pages= 516-30 | pmid=14347873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14347873 }} </ref><ref name="pmid4956920">{{cite journal| author=Beck EA, Charache P, Jackson DP| title=A new inherited coagulation disorder caused by an abnormal fibrinogen ('fibrinogen Baltimore'). | journal=Nature | year= 1965 | volume= 208 | issue= 5006 | pages= 143-5 | pmid=4956920 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4956920 }} </ref> Later, in the 1990s, the more common mutations associated with primary hypercoagulable states were identified.<ref name="pmid8164741">{{cite journal| author=Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H et al.| title=Mutation in blood coagulation factor V associated with resistance to activated protein C. | journal=Nature | year= 1994 | volume= 369 | issue= 6475 | pages= 64-7 | pmid=8164741 | doi=10.1038/369064a0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8164741 }} </ref><ref name="pmid8916933">{{cite journal| author=Poort SR, Rosendaal FR, Reitsma PH, Bertina RM| title=A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. | journal=Blood | year= 1996 | volume= 88 | issue= 10 | pages= 3698-703 | pmid=8916933 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8916933 }} </ref>

==Classification==
Thrombophilias may be classified into three groups: '''inherited or primary hypercoagulable states''', '''acquired or secondary hypercoagulable states''', or '''mixed/unknown'''. Certain conditions are associated with greater thrombotic risks and both venous and arterial clots.

==Pathophysiology==
The pathogenesis of thrombophilia is multi-factorial. It is characterized by hypercoagulability, which by itself or in synergy with '''endothelial injury''' or '''stasis''' ([[Virchow's_triad|Virchow's Triad]]) can predispose to [[thrombus|clot formation]]. Multiple [[Thrombophilia_classification|genetic mutations and predisposing conditions]] have been associated with the increased risk of [[thrombosis]] due to abnormalities in the [[coagulation]] cascade.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The most common genes involved in the pathogenesis of acquired thrombophilias are [[Factor V Leiden]] and '''[[prothrombin]] gene mutations'''.

==Causes==
Thrombophilia may be caused by either [[Thrombophilia_classification|acquired, inherited, or, more commonly, a combination of both conditions]]. The most frequent forms of inherited thrombophilia are Factor V Leiden (20-50% prevalence in patients with recurrent venous thrombosis) and prothrombon G20210A (5-20% prevalence in patients with recurrent venous thrombosis).<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

==Differentiating Inherited Thrombophilia from other Diseases==
Inherited thrombophilia must be differentiated from acquired thrombophilia, as it may influence the selection and duration of [[Anticoagulant|anticoagulation]]. Inherited thrombophilias should be suspected in patients with the certain [[Thrombophilia_history_and_symptoms|clinical presentations]].<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> [[Thrombophilia screening|Screening]] for inherited thrombophilias is controversial and should be performed in the appropriate clinical context.<ref name="pmid21340752">{{cite journal| author=Middeldorp S| title=Evidence-based approach to thrombophilia testing. | journal=J Thromb Thrombolysis | year= 2011 | volume= 31 | issue= 3 | pages= 275-81 | pmid=21340752 | doi=10.1007/s11239-011-0572-y | pmc=3056012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21340752 }} </ref>

==Epidemiology and Demographics==
Due to the multitude and complexity of inherited thrombophilias, the true [[prevalence]] is unknown, and current data may be providing an underestimate. Comparison among different epidemiologic studies becomes difficult due to variation in study design and inclusion criteria. Prevalence of common inherited thrombophilias is variable among both healthy patients and patients with recurrent [[thrombosis]]. According to epidemiologic and modeling studies obtained from certain sources, the prevalence of inherited thrombophilias was estimated to be between 0.01-7% in caucasians.<ref name="pmid26780744">{{cite journal| author=Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M et al.| title=Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 154-64 | pmid=26780744 | doi=10.1007/s11239-015-1316-1 | pmc=4715840 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780744 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> In certain studies, the prevalence of inherited thrombophilias, specifically, '''activated protein C resistance''' and '''prothrombin G20210A''', rises to approximately 10-60% in patients with documented venous thrombosis compared to less than 10% among controls.<ref name="pmid9669991">{{cite journal| author=Margaglione M, Brancaccio V, Giuliani N, D'Andrea G, Cappucci G, Iannaccone L et al.| title=Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant. | journal=Ann Intern Med | year= 1998 | volume= 129 | issue= 2 | pages= 89-93 | pmid=9669991 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9669991 }} </ref><ref name="pmid7877648">{{cite journal| author=Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP| title=Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. | journal=N Engl J Med | year= 1995 | volume= 332 | issue= 14 | pages= 912-7 | pmid=7877648 | doi=10.1056/NEJM199504063321403 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7877648 }} </ref><ref name="pmid7902898">{{cite journal| author=Koster T, Rosendaal FR, de Ronde H, Briët E, Vandenbroucke JP, Bertina RM| title=Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. | journal=Lancet | year= 1993 | volume= 342 | issue= 8886-8887 | pages= 1503-6 | pmid=7902898 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7902898 }} </ref> The incidence of inherited thrombophilia in incident venous thrombosis is approximately 150-840 per 100,000 person years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref> The incidence of inherited thrombophilia in recurrent venous thrombosis is approximately 3,500-10,500 per 100,000 person-years.<ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref>

===Age===
Patients of all age groups may develop thrombophilias. Acquired thrombophilias are more commonly observed among elderly patients (age > 60) as age is a risk factor for thrombosis. Inherited thrombophilias can be seen among young patients aged <40-55 years old.

===Gender===
Epidemiologic studies have provided mixed results regarding the effect of gender on venous thrombosis. Certain groups observed increased risk of thrombosis in younger females and older males, whereas other groups found similar frequencies in both genders.<ref name="pmid12814979">{{cite journal| author=White RH| title=The epidemiology of venous thromboembolism. | journal=Circulation | year= 2003 | volume= 107 | issue= 23 Suppl 1 | pages= I4-8 | pmid=12814979 | doi=10.1161/01.CIR.0000078468.11849.66 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12814979 }} </ref> A prospective follow up study performed by Christiansen et al, revealed an age corrected hazard ratio of 2.7 of recurrent thrombosis in male patients with inherited thrombophilias compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref> In patients with inherited thrombophilias, a prospective follow up study performed by Christiansen et al revealed an age corrected hazard ratio of 2.7 for recurrent thrombosis in male patients compared to women.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref>

===Race===
The factor V leiden G1691A and prothrombin G20210A mutations are exceedingly rare in non-white populations.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

==Risk Factors==
The most common risk factors in the development of acquired thrombophlias are trauma, surgery, immobility, pregnancy, estrogen therapy, and age. The most common risk factors in the development of inherited thrombophilias are genetic mutations in factor V leiden and prothrombon G20210A.

== Natural History, Complications and Prognosis==
The annual thrombotic risks are variable and depend on the underlying thrombophilia.<ref name="pmid11529700">{{cite journal| author=Bauer KA| title=The thrombophilias: well-defined risk factors with uncertain therapeutic implications. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 5 | pages= 367-73 | pmid=11529700 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11529700 }} </ref> If left untreated, the annual incidence of incident thrombosis in asymptomatic patients with [[Factor V Leiden]] and ([https://en.wikipedia.org/wiki/Prothrombin_G20210A Prothrombin G20210A]) is low (<0.06%) .<ref name="pmid15254285">{{cite journal| author=Bates SM, Ginsberg JS| title=Clinical practice. Treatment of deep-vein thrombosis. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 3 | pages= 268-77 | pmid=15254285 | doi=10.1056/NEJMcp031676 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15254285 }} </ref> The risk is approximately equivalent to treatment with [[Oral_contraceptive|oral contraceptives (OCPs)]]. Whereas the annual incidence of significant bleeds is approximately 2-3%.<ref name="pmid14644891">{{cite journal| author=Linkins LA, Choi PT, Douketis JD| title=Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 11 | pages= 893-900 | pmid=14644891 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14644891 }} </ref> Studies performed by Christiansen et al and Baglin et al revealed that inherited thrombophilia from factor V leiden and prothrombin G20210A did not predict for recurrent thrombosis.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid12932383">{{cite journal| author=Baglin T, Luddington R, Brown K, Baglin C| title=Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. | journal=Lancet | year= 2003 | volume= 362 | issue= 9383 | pages= 523-6 | pmid=12932383 | doi=10.1016/S0140-6736(03)14111-6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12932383 }} </ref> Christiansen et al and De Stefano et al observed a mild increased risk for recurrent thrombosis in patients with [[Protein_C|protein C]], [[Protein_S|protein S]], and [[antithrombin]] deficiency.<ref name="pmid15900005">{{cite journal| author=Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR| title=Thrombophilia, clinical factors, and recurrent venous thrombotic events. | journal=JAMA | year= 2005 | volume= 293 | issue= 19 | pages= 2352-61 | pmid=15900005 | doi=10.1001/jama.293.19.2352 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15900005 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213089 Review in: Evid Based Med. 2006 Apr;11(2):59] </ref><ref name="pmid16670075">{{cite journal| author=De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A et al.| title=The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. | journal=Haematologica | year= 2006 | volume= 91 | issue= 5 | pages= 695-8 | pmid=16670075 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16670075 }} </ref> OCPs, hormone replacement therapy, and pregnancy can significantly increase thrombotic risk in patients with thrombophilia.<ref name="pmid18501222">{{cite journal| author=Dalen JE| title=Should patients with venous thromboembolism be screened for thrombophilia? | journal=Am J Med | year= 2008 | volume= 121 | issue= 6 | pages= 458-63 | pmid=18501222 | doi=10.1016/j.amjmed.2007.10.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18501222 }} </ref> Certain high risk thrombophilias require indefinate [[anticoagulant|anticoagulation]].

== Diagnosis ==
===Diagnostic Criteria===
The diagnosis of an inherited thrombophilia is made with specific [[Thrombophilia_laboratory_findings|laboratory tests]] for each inherited condition.

=== Symptoms ===
Common symptoms of thrombophilias may include symptoms of [[Deep venous thrombosis]], [[Pulmonary embolus]], and superficial venous thrombosis.

=== Physical Examination ===
Physical examination of patients with thrombophilia is usually remarkable for signs of [[Deep_vein_thrombosis_physical_examination|deep venous thrombosis]], [[Pulmonary_embolism_physical_examination|pulmonary thrombosis]], [[Renal_vein_thrombosis|renal vein thrombosis]], [[Cerebral_venous_sinus_thrombosis_physical_examination|cerebral vein thrombosis]], [[Superficial_vein_thrombosis|superficial vein thrombosis]], arterial thrombosis, [[Portal_hypertension_physical_examination|portal hypertension]] which can be sign of [https://en.wikipedia.org/wiki/Portal_vein_thrombosis| portal vein thrombosis], [[Warfarin_necrosis|warfarin skin necrosis]], or [https://en.wikipedia.org/wiki/Livedo_reticularis livedo reticularis].<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

=== Screening ===
According to the American Society of Hematology, screening for inherited thrombophilias in adult patients with venous [[thrombosis]] in the setting of major transient risk factors which include surgery, trauma, or prolonged immobility is not recommended.<ref name="pmid24319155">{{cite journal| author=Hicks LK, Bering H, Carson KR, Kleinerman J, Kukreti V, Ma A et al.| title=The ASH Choosing Wisely®campaign: five hematologic tests and treatments to question. | journal=Hematology Am Soc Hematol Educ Program | year= 2013 | volume= 2013 | issue= | pages= 9-14 | pmid=24319155 | doi=10.1182/asheducation-2013.1.9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24319155 }} </ref> However, given the [[Thrombophilia_natural_history,_complications_and_prognosis|associated risks]] for recurrent thrombosis, patients who have significant risk factors including a positive family history or concurrent treatment with hormonal therapies should seek expert consultation.

=== Laboratory Findings ===
Laboratory findings consistent with the diagnosis of inherited thrombophilias include specific [[Thrombophilia_laboratory_findings|laboratory findings]] associated with each inherited thrombophilia.<ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref>

===Imaging Findings===
[[Ultrasound|Ultrasongraphy]], [https://en.wikipedia.org/wiki/Computed_tomography_angiography| computed tomography angiography (CTA or CT Angiography)], [https://en.wikipedia.org/wiki/Magnetic_resonance_angiography| magnetic resonance angiography (MRA or MR Angiography)] and [[Angiogram|projectional angiography]] may be diagnostic of acute thrombosis, which is associated with the diagnosis of thrombophilia.

== Treatment ==
=== Medical Therapy ===
The [[Thrombophilia_medical_therapy|treatment]] for thrombophilia depends on the underlying hypercoagulable state and the clinical presentation.<ref name=?>DeLoughery TG. Hemostasis and Thrombosis: Springer International Publishing; 2014.</ref><ref name="pmid24421360">{{cite journal| author=Cohoon KP, Heit JA| title=Inherited and secondary thrombophilia. | journal=Circulation | year= 2014 | volume= 129 | issue= 2 | pages= 254-7 | pmid=24421360 | doi=10.1161/CIRCULATIONAHA.113.001943 | pmc=3979345 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24421360 }} </ref><ref name="pmid11309638">{{cite journal| author=Seligsohn U, Lubetsky A| title=Genetic susceptibility to venous thrombosis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 16 | pages= 1222-31 | pmid=11309638 | doi=10.1056/NEJM200104193441607 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11309638 }} </ref> The mainstay of therapy for thrombophilia is [[anticoagulation]] with either [[warfarin]], [[Low_molecular_weight_heparin|low molecular weight heparin]], [[Direct_Xa_inhibitor|direct Xa inhibitors]], or [[Direct_thrombin_inhibitor|direct thrombin inhibitors]].<ref name="pmid26780738">{{cite journal| author=Streiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R et al.| title=Guidance for the treatment of deep vein thrombosis and pulmonary embolism. | journal=J Thromb Thrombolysis | year= 2016 | volume= 41 | issue= 1 | pages= 32-67 | pmid=26780738 | doi=10.1007/s11239-015-1317-0 | pmc=4715858 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26780738 }} </ref><ref name="pmid18805965">{{cite journal| author=Martinelli I, Franchini M, Mannucci PM| title=How I treat rare venous thromboses. | journal=Blood | year= 2008 | volume= 112 | issue= 13 | pages= 4818-23 | pmid=18805965 | doi=10.1182/blood-2008-07-165969 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18805965 }} </ref><ref name="pmid23789890">{{cite journal| author=De Stefano V, Grandone E, Martinelli I| title=Recommendations for prophylaxis of pregnancy-related venous thromboembolism in carriers of inherited thrombophilia. Comment on the 2012 ACCP guidelines. | journal=J Thromb Haemost | year= 2013 | volume= 11 | issue= 9 | pages= 1779-81 | pmid=23789890 | doi=10.1111/jth.12330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23789890 }} </ref> Treatment should be tailored to the individual patient. The risks and benefits, required monitoring, and costs associated with each form of anticoagulation should be discussed with the patient prior to initiation of therapy. All patients on anticoagulation should be monitored for bleeding.

=== Surgery ===
*Surgery is not required for treatment for thrombophilia
*[[IVC_filter|IVC filter]] placement may be indicated in certain scenarios:<ref> Inferior Vena Cava Filters. Medscape (2015). URL Accessed on July 17, 2016</ref>
**Contraindications to or complications from [[anticoagulation]]
**Recurrent thrombosis on anticoagulation, or failure to acheive therapeutic anticoagulation levels

=== Prevention ===
*[[Thrombophilia_medical_therapy|Prophylaxis]] may be indicated for thrombophilia in certain scenarios
*Once diagnosed and successfully treated, patients with thrombophilia are followed-up routinely to monitor anticoagulation and clinically if thrombosis recurrs

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Hematology]]
[[Category:Primary care]]

Thrombophilia other diagnostic studies

2016-07-18T18:24:37Z

Asiri Saumya Ediriwickrema: /* Overview */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
The diagnosis of an inherited thrombophilia is made with specific [[Thrombophilia_laboratory_findings|laboratory tests]] for each inherited condition.

==Other diagnostic studies==
*The diagnosis of an inherited thrombophilia is made with specific [[Thrombophilia_laboratory_findings|laboratory tests]] for each inherited condition.

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia other imaging findings

2016-07-18T18:23:58Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[https://en.wikipedia.org/wiki/Ventilation/perfusion_scan| Ventilation perfusion scans] may be diagnostic of acute [[Pulmonary_embolism| pulmonary embolism]].

==Other imaging findings==
*[https://en.wikipedia.org/wiki/Ventilation/perfusion_scan| Ventilation perfusion scans] may be diagnostic of acute [[Pulmonary_embolism| pulmonary embolism]].

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia other imaging findings

2016-07-18T18:23:21Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
*[https://en.wikipedia.org/wiki/Ventilation/perfusion_scan| Ventilation perfusion scans] may be diagnostic of acute [[Pulmonary_embolism| pulmonary embolism]].

==Other imaging findings==
*[https://en.wikipedia.org/wiki/Ventilation/perfusion_scan| Ventilation perfusion scans] may be diagnostic of acute [[Pulmonary_embolism| pulmonary embolism]].

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia echocardiography or ultrasound

2016-07-18T18:22:33Z

Asiri Saumya Ediriwickrema: /* Ultrasound */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Ultrasound|Ultrasongraphy]] may be diagnostic of acute [[Deep_vein_thrombosis_ultrasound|thrombosis]], and is associated with the diagnosis of thrombophilia

==Ultrasound==
*[[Ultrasound|Ultrasongraphy]] may be diagnostic of acute [[Deep_vein_thrombosis_ultrasound|thrombosis]], and is associated with the diagnosis of thrombophilia

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia echocardiography or ultrasound

2016-07-18T18:22:09Z

Asiri Saumya Ediriwickrema: /* Overview */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Ultrasound|Ultrasongraphy]] may be diagnostic of acute [[Deep_vein_thrombosis_ultrasound|thrombosis]], and is associated with the diagnosis of thrombophilia

==Ultrasound==
*[[Ultrasound|Ultrasongraphy]] is used to identify [[Deep_vein_thrombosis_ultrasound|thrombosis]], and is associated with the diagnosis of thrombophilia

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia MRI

2016-07-18T18:21:20Z

Asiri Saumya Ediriwickrema: /* MRI */

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[[Magnetic_resonance_imaging|Magnetic resonance imaging (MRI)]] is usually not indicated for diagnosis and monitoring of thrombophilias.

==MRI==
*[https://en.wikipedia.org/wiki/Magnetic_resonance_angiography| MR angiography] may be diagnostic of [[Pulmonary_embolism_MRI|pulmonary embolism]], [[Deep_vein_thrombosis_MRI|deep vein thrombosis]], or [[Cerebral_venous_sinus_thrombosis_MRI|cerebral venous thrombosis]]

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}

Thrombophilia CT

2016-07-18T18:20:25Z

Asiri Saumya Ediriwickrema:

__NOTOC__
{{Thrombophilia}}
{{CMG}} {{AE}} {{asiri}}

==Overview==
[https://en.wikipedia.org/wiki/Computed_tomography_angiography| Computed tomography angiography (CTA or CT Angiography)] may be diagnostic of acute thrombosis, and is associated with the diagnosis of thrombophilia

==CT==
*A Chest CTA is the gold standard for the diagnosis of [[Pulmonary_embolism_CT|pulmonary embolism]]
*CT scans can also be used to diagnose [[Deep_vein_thrombosis_CT|deep vein thrombosis]], [[Renal_vein_thrombosis|renal vein thrombosis]], and [[Cerebral_venous_sinus_thrombosis_CT|cerebral venous thrombosis]]

==References==
{{reflist|2}}

[[Category:Hematology]]

{{WH}}
{{WS}}