Bleeding disorder resident survival guide: Difference between revisions

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__NOTOC__
__NOTOC__


{{CMG}}; {{AE}} {{JA}}
{{CMG}}; {{AE}} {{JA}}<br>
{{SK}} Approach to bleeding diathesis, Bleeding diathesis workup, Bleeding diathesis management
== Overview ==
== Overview ==
The bleeding disorder can be due to coagulopathy, [[platelet]] dysfunction, or vessel [[pathology]]. History of the site, duration, associated symptoms, and a thorough physical exam to evaluate the type of bleeding ([[subcutaneous]] vs deep [[tissue]]) are essential to [[diagnosis]]. [[Screening]] tests include [[CBC]], [[PT]], [[aPTT]], [[PFA-100]].
A bleeding disorder can be due to [[coagulopathy]], [[platelet]] dysfunction, or vessel [[pathology]]. They can be genetic or acquired. History of the site, duration, associated [[symptoms]], and a thorough physical exam to evaluate the type of bleeding ([[subcutaneous]] vs deep [[tissue]]) are essential to [[diagnosis]]. [[Screening]] tests include [[CBC]] with [[peripheral blood smear]], [[platelet]] count, [[PT]], [[aPTT]], [[PFA-100]]. Management depends upon the type of [[disorder]], severity, and active [[bleeding]]. [[Plasma]] exchange, [[fresh frozen plasma]], and factor replacement are the main treatment options available.  The initial clinical impression based on the baseline screening tests should direct specialized laboratory tests to save time, effort, and money.


== Causes ==
== Causes ==
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{{familytree | | F01 | | | | F02 | | | | | | | | | | | | | F01=Hemorrhagic disorders|F02=Hypercoaguable disease}}
{{familytree | | F01 | | | | F02 | | | | | | | | | | | | | F01=Hemorrhagic disorders|F02=Hypercoaguable disease}}
{{familytree | | |!| | | | | |!| | | | | | | | | | | |}}
{{familytree | | |!| | | | | |!| | | | | | | | | | | |}}
{{familytree | | G01 | | | | G02 | | | | | | | | | | | | |G01=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[Factor VIII deficiency]]<br>
{{familytree | | G01 | | | | G02 | | | | | | | | | | | | |G01=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[Factor VIII deficiency]] ([[Hemophilia A overview|Hemophilia A]])<br>
❑ [[Factor IX Deficiency]]<br>
❑ [[Factor IX Deficiency]] ([[Hemophilia B overview|Hemophilia B]])<br>
❑ [[Von Willebrand disease|Von Willebrand factor deficiency]]<br>
❑ [[Von Willebrand disease|Von Willebrand factor deficiency]]<br>
❑ Factor XI deficiency <br>
[[Factor XI]] deficiency ([[Hemophilia C]]) <br>
❑ Factor II, V, VII, X deficiency (Common Pathway Proteins)<br>
❑ Factor II, V, VII, X deficiency (Common Pathway Proteins)<br>
❑ [[Factor XIII]] deficiency and [[fibrinogen]] deficiency|G02=<div style="float: left; text-align: left; width: 20em; padding:1em;"><br>❑ [[Antithrombin III deficiency]]<br>
❑ [[Factor XIII]] deficiency and [[fibrinogen]] deficiency|G02=<div style="float: left; text-align: left; width: 20em; padding:1em;"><br>❑ [[Antithrombin III deficiency]]<br>
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== Diagnosis ==
== Diagnosis ==


The algorithm illustrates the approach to the diagnosis of bleeding disorder.<ref name="pmid23012146">{{cite journal |vauthors=Bashawri LA, Ahmed MA |title=The approach to a patient with a bleeding disorder: for the primary care physician |journal=J Family Community Med |volume=14 |issue=2 |pages=53–8 |date=May 2007 |pmid=23012146 |pmc=3410146 |doi= |url=}}</ref><ref name="pmid16304414">{{cite journal |vauthors=Hayward CP |title=Diagnosis and management of mild bleeding disorders |journal=Hematology Am Soc Hematol Educ Program |volume= |issue= |pages=423–8 |date=2005 |pmid=16304414 |doi=10.1182/asheducation-2005.1.423 |url=}}</ref><ref name="pmid1912663">{{cite journal |vauthors=Blanchette VS, Sparling C, Turner C |title=Inherited bleeding disorders |journal=Baillieres Clin Haematol |volume=4 |issue=2 |pages=291–332 |date=April 1991 |pmid=1912663 |doi=10.1016/s0950-3536(05)80162-3 |url=}}</ref><br>
The algorithm illustrates the approach to the diagnosis of bleeding disorder.<ref name="pmid23012146">{{cite journal |vauthors=Bashawri LA, Ahmed MA |title=The approach to a patient with a bleeding disorder: for the primary care physician |journal=J Family Community Med |volume=14 |issue=2 |pages=53–8 |date=May 2007 |pmid=23012146 |pmc=3410146 |doi= |url=}}</ref><ref name="pmid16304414">{{cite journal |vauthors=Hayward CP |title=Diagnosis and management of mild bleeding disorders |journal=Hematology Am Soc Hematol Educ Program |volume= |issue= |pages=423–8 |date=2005 |pmid=16304414 |doi=10.1182/asheducation-2005.1.423 |url=}}</ref><ref name="pmid1912663">{{cite journal |vauthors=Blanchette VS, Sparling C, Turner C |title=Inherited bleeding disorders |journal=Baillieres Clin Haematol |volume=4 |issue=2 |pages=291–332 |date=April 1991 |pmid=1912663 |doi=10.1016/s0950-3536(05)80162-3 |url=}}</ref><ref name="Favaloro2002">{{cite journal|last1=Favaloro|first1=Emmanuel J.|title=Clinical application of the PFA-100®|journal=Current Opinion in Hematology|volume=9|issue=5|year=2002|pages=407–415|issn=1065-6251|doi=10.1097/00062752-200209000-00004}}</ref><ref name="Harrison2005">{{cite journal|last1=Harrison|first1=Paul|title=The role of PFA-100R testing in the investigation and management of haemostatic defects in children and adults|journal=British Journal of Haematology|volume=130|issue=1|year=2005|pages=3–10|issn=0007-1048|doi=10.1111/j.1365-2141.2005.05511.x}}</ref><br>
Abbreviations: '''HEENT:''' [[Head, Eyes, Ears. Nose, and Throat exam]]; '''CBC:''' [[CBC|Complete blood count]]; '''APTT''' [[Partial thromboplastin time]]; '''CMP:''' [[Comprehensive metabolic panel]]; '''LFTs:'''[[Liver function tests]] </span><br>
Abbreviations: '''HEENT:''' [[Head, Eyes, Ears. Nose, and Throat exam]]; '''CBC:''' [[CBC|Complete blood count]]; '''APTT''' [[Partial thromboplastin time]]; '''CMP:''' [[Comprehensive metabolic panel]]; '''LFTs:'''[[Liver function tests]] </span><br>
<span style="font-size:85%">Boxes in red signify that an urgent management is needed.<br>
<span style="font-size:85%">Boxes in red signify that an urgent management is needed.<br>
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❑ [[Gastrointestinal system]] exam includes [[oral examination]], [[abdominal examination]], and [[digital rectal exam]]. <br>
❑ [[Gastrointestinal system]] exam includes [[oral examination]], [[abdominal examination]], and [[digital rectal exam]]. <br>
❑ [[Limb (anatomy)|Extremities]] exam<br>
❑ [[Limb (anatomy)|Extremities]] exam<br>
❑ Skin exam: Evaluate for the [[petechie]], [[bruises]], [[hemorrhages]]. Location, symmetry, and pattern are important.}}
❑ Skin exam: Evaluate for [[petechie]], [[bruises]], [[hemorrhages]]. Location, symmetry, and pattern are important.}}
{{familytree | | | | | | | | | | |!| | | | | | |}}
{{familytree | | | | | | | | | | |!| | | | | | |}}
{{familytree | | | | | | | | | | |!| | | | | | | }}
{{familytree | | | | | | | | | | |!| | | | | | | }}
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❑ [[Vitamin K deficiency]]<br>
❑ [[Vitamin K deficiency]]<br>
❑ Early [[anticoagulation]] therapy|D03=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ Check [[thrombin time]]|D04=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[ITP|Idiopathic Thrombocytopenic Purpura]] (ITP)<br>❑ Hereditary [[platelet]] disorder<br>❑ [[Bone marrow]] failure|D05= Check [[PFA-100]]}}
❑ Early [[anticoagulation]] therapy|D03=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ Check [[thrombin time]]|D04=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[ITP|Idiopathic Thrombocytopenic Purpura]] (ITP)<br>❑ Hereditary [[platelet]] disorder<br>❑ [[Bone marrow]] failure|D05= Check [[PFA-100]]}}
{{familytree | | | | |!| | |!| | |,|-|^|-|.| | | | |!| | |,|-|^|-|-|.|}}
{{familytree | | | | | | | | | | |,|-|^|-|.| | | | | | | |,|-|^|-|-|.|}}
{{familytree | | | | |!| | |!| | |!| | | |!| | | | |!| | |!| | | | |!| |}}
{{familytree | | | | | | | | | | |!| | | |!| | | | | | | |!| | | | |!| |}}
{{familytree | | | E01 | | E02 | | E03 | | E04 | | E05 | | E06 | | E07 | | | | |E03=Prolonged|E04=Normal}}
{{familytree | | | | | | | | | E03 | | E04 | | | | | | E06 | | | E07 | | | | |E03=Prolonged|E04=Normal|E06=Prolonged closure time|E07=Normal}}
{{familytree | | | | | | | | | | |!| | | |!| | | | |!| | | | | | | |!| |}}
{{familytree | | | | | | | | | | |!| | | |!| | | | | | |!| | | | |!| | |}}
{{familytree | | | | | | | | | | | F01 | | F02 | | | |F01=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[Fibrinogen]] deficiency<br>❑ [[Liver]] disease<br>❑ [[Heparin]]|F02=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[Factor II]], [[factor V]], [[factor X]] deficiency<br>❑ [[Vitamin K]] deficiency<br> ❑ [[Liver]] disease}}
{{familytree | | | | | | | | | | | F01 | | F02 | | | | F03 | | | F04 | | | | | | | |F01=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[Fibrinogen]] deficiency<br>❑ [[Liver]] disease<br>❑ [[Heparin]]|F02=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[Factor II]], [[factor V]], [[factor X]] deficiency<br>❑ [[Vitamin K]] deficiency<br> ❑ [[Liver]] disease|F03=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[CBC|Full blood count]]<br>
❑ [[vWF]] screen<br>
❑ [[Platelet]] function testing|F04= <div style="float: left; text-align: left; width: 20em; padding:1em;">High clinical suspician}}
{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | | |!| | |}}
{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | | G01 | | |G01=<div style="float: left; text-align: left; width: 20em; padding:1em;">❑ [[vWF]] screen<br>❑ [[Platelet]] function testing (required to exclude abnormal [[platelet]] function)}}
{{familytree/end}}
{{familytree/end}}


== Treatment ==
== Management ==
The following tables illustrate the treatment to common bleeding disorders.<ref name="pmid19536318">{{cite journal |vauthors=Powell JS |title=Recombinant factor VIII in the management of hemophilia A: current use and future promise |journal=Ther Clin Risk Manag |volume=5 |issue=2 |pages=391–402 |date=April 2009 |pmid=19536318 |pmc=2697540 |doi=10.2147/tcrm.s4412 |url=}}</ref><ref name="pmid23656742">{{cite journal |vauthors=Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, De Robertis E, Filipescu DC, Fries D, Görlinger K, Haas T, Imberger G, Jacob M, Lancé M, Llau J, Mallett S, Meier J, Rahe-Meyer N, Samama CM, Smith A, Solomon C, Van der Linden P, Wikkelsø AJ, Wouters P, Wyffels P |title=Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology |journal=Eur J Anaesthesiol |volume=30 |issue=6 |pages=270–382 |date=June 2013 |pmid=23656742 |doi=10.1097/EJA.0b013e32835f4d5b |url=}}</ref><ref name="pmid25535422">{{cite journal |vauthors=Gopinath R, Sreekanth Y, Yadav M |title=Approach to bleeding patient |journal=Indian J Anaesth |volume=58 |issue=5 |pages=596–602 |date=September 2014 |pmid=25535422 |pmc=4260306 |doi=10.4103/0019-5049.144664 |url=}}</ref><ref name="pmid27913543">{{cite journal |vauthors=Meeks SL, Batsuli G |title=Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches |journal=Hematology Am Soc Hematol Educ Program |volume=2016 |issue=1 |pages=657–662 |date=December 2016 |pmid=27913543 |pmc=6142469 |doi=10.1182/asheducation-2016.1.657 |url=}}</ref><ref name="pmid28350321">{{cite journal |vauthors=Napolitano M, Siragusa S, Mariani G |title=Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy |journal=J Clin Med |volume=6 |issue=4 |pages= |date=March 2017 |pmid=28350321 |pmc=5406770 |doi=10.3390/jcm6040038 |url=}}</ref><ref name="pmid19143930">{{cite journal |vauthors=Hayward CP, Pai M, Liu Y, Moffat KA, Seecharan J, Webert KE, Cook RJ, Heddle NM |title=Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments |journal=J Thromb Haemost |volume=7 |issue=4 |pages=676–84 |date=April 2009 |pmid=19143930 |doi=10.1111/j.1538-7836.2009.03273.x |url=}}</ref><ref name="UprichardPerry2002">{{cite journal|last1=Uprichard|first1=James|last2=Perry|first2=David J.|title=Factor X deficiency|journal=Blood Reviews|volume=16|issue=2|year=2002|pages=97–110|issn=0268960X|doi=10.1054/blre.2002.0191}}</ref><ref name="pmid6547008">{{cite journal |vauthors=Bertina RM, Broekmans AW, Krommenhoek-van Es C, van Wijngaarden A |title=The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency |journal=Thromb. Haemost. |volume=51 |issue=1 |pages=1–5 |date=February 1984 |pmid=6547008 |doi= |url=}}</ref><ref name="pmid8165605">{{cite journal| author=Faioni EM, Franchi F, Asti D, Sacchi E, Bernardi F, Mannucci PM| title=Resistance to activated protein C in nine thrombophilic families: interference in a protein S functional assay. | journal=Thromb Haemost | year= 1993 | volume= 70 | issue= 6 | pages= 1067-71 | pmid=8165605 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8165605  }} </ref><ref name="BrownKouides2008">{{cite journal|last1=Brown|first1=D. L.|last2=Kouides|first2=P. A.|title=Diagnosis and treatment of inherited factor X deficiency|journal=Haemophilia|volume=14|issue=6|year=2008|pages=1176–1182|issn=13518216|doi=10.1111/j.1365-2516.2008.01856.x}}</ref>
{| style="border: 0px; font-size: 100%; margin: 3px;" align=center
|+
! style="width: 70px; background: #4479BA;" | {{fontcolor|#FFF|'''Disorder'''}}
! style="width: 300px; background: #4479BA;" | {{fontcolor|#FFF|'''Labs'''}}
! style="width: 300px; background: #4479BA;" | {{fontcolor|#FFF|'''Treatment'''}}
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Factor VII deficiency]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Measure [[factor VII]] coagulant activity for isolated prolonged [[PT]]
*Diagnosis is confirmed with a repeat [[factor VII]] assay
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Consider the type (such as type I: quantitative defects, type II: qualitative defects, for the management.
*Replacement therapy: Recombinant [[factor VII|FVIIa]] (rFVIIa) is most used. Median dosage of 60 μg/kg is safe for [[bleeding]] such as [[hematomas]], [[hemarthrosis]], and [[epistaxis]].
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Hemophilia A overview|Hemophilia A]] and [[Hemophilia B overview|Hemophilia B]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Factor VIII]] and [[factor IX]] assay
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Factor VIII]] concentrate (20-50 IU/ml)
*BPAs (bypass agents) help get around [[factor VIIa]] and [[Factor IX]] to generate [[thrombin]].
*[[Immunity|Immune]] tolerance induction (ITI) is the standard of care for inhibitor eradication predominantly among [[patients]] with severe [[Hemophilia A overview|hemophilia A]].
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Factor X deficiency]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Prolonged [[PT]] and [[APTT]]
*[[Factor X]] levels
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*No specific [[factor X]] replacement product is yet readily available.
*[[Bleeding]] or [[surgery]] preparation: Administer [[fresh frozen plasma]] and [[prothrombin concentrate|prothrombin complex concentrates]].
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Hemophilia C]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Factor XI]] assay
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Fresh frozen plasma]]
*[[Factor XI]] is rarely required
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Von Willebrand disease]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Factor VIII]], [[Protein C]], [[VWF]] Ag, [[VWF|VWi]]Cof
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Bleeding prevention: 0.3 mcg/kg [[Desmopressin (injection)|desmopressin acetate]] (DDAVP), 90 min before [[surgery]] helps prevent [[bleeding]] (increases the level of [[Von Willebrand factor|VWFAg]] and [[factor VIII]] to normal).
* Minor bleed: [[Desmopressin (injection)|desmopressin acetate]] is the first-line agent. [[Tranexamic acid]] can be used.
* Major bleed: Replacing [[VWF]] and utilizing plasma-derived products. [[Antifibrinolytic]] drugs may be utilized as a [[hemostasis|hemostatic]] adjunct. Transfuse [[platelets]] only if other treatments fail.
* [[Factor VIII]] concentrates and [[plasma]] products also help overcome bleeding.
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Microangiopathic hemolytic anemia]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Platelet count]]] (also look for the clinical signs such as neurological deficits among [[TTP]] and [[renal dysfunction]] among [[HUS]] patients.
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Total [[plasma]] exchange, [[cryoprecipitate]] lacking [[HMV VW]] multimers.
*0.4 mg/kg [[IVIG]] for five days with a target [[platelet count]] to be 80,000.
*Among [[prennancy|pregnant]] females with [[TTP]]/ [[HUS]] administer [[FFP]] and avoid [[RPR]].
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Glanzmann's thrombasthenia]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Platelet aggregation]] assays.
*Confirmed through [[flow cytometry]].
*To read more about diagnosis [[Glanzmann's thrombasthenia diagnostic study of choice|click here]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Desmopressin]] (DDAVP): Increases the levels of [[tissue plasminogen activator]] (tPA), [[FVIII]], and [[von Willebrand factor]] ([[VWF]]) in [[plasma]].
*[[Rituximab]]
*[[Hematopoietic stem cell transplantation]]
*[[Gene therapy]]
*[[Platelet transfusion]]
*To read more about the treatment, [[Glanzmann's thrombasthenia medical therapy|click here]].
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Bernard-Soulier syndrome]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[PFA-100]] is used for [[screening]].
* Prolonged [[bleeding time]].
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Supportive care.
*Pharmacotherapy for [[bleeding]] episodes such as [[tranexamic acid]] or ε-[[aminocaproic acid]], [[platelet transfusion]], and [[Desmopressin]] (DDAVP).
*To read more about the management [[Bernard-Soulier syndrome#Treatment|click here]].
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Thrombocytopenia]] of [[pregnancy]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Platelet count]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Mild: [[Corticosteroids]]
*Severe: Intervenous [[methyl prednisolone]].
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[SLE]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Platelet count]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[RPR]]
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | Liver disease
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[LFTs]], [[APTT]], [[platelet count]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Vitamin K]] if the [[patient]] has [[vitamin K]] deficiency.
*Treat per deficiency.
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Antithrombin III deficiency]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Antithrombin III]] levels
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Anticoagulants]]
*[[Antithrombin]] concentrate
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Protein C deficiency]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Functional assays such as [[aPTT]] based assay, [[factor Xa]] based [[enzyme|anzymatic]] assay to determine the function of [[protein C]].
*[[Antigenic]] determination of [[protein C]] levels.
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Pharmacotherapy is recommended among [[patients]] with [[Warfarin]]-induced skin [[necrosis]], neonatal [[purpura]] fulminans and [[pulmonary embolism]].<ref name="pmid3754407">{{cite journal |vauthors=Zauber NP, Stark MW |title=Successful warfarin anticoagulation despite protein C deficiency and a history of warfarin necrosis |journal=Ann. Intern. Med. |volume=104 |issue=5 |pages=659–60 |date=May 1986 |pmid=3754407 |doi= |url=}}</ref>
*To read more about the treatment [[Protein C deficiency#Treatment|click here]].
|-
| style="padding: 0 5px; background: #DCDCDC; text-align: left;" | [[Protein S deficiency]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*Free protein S [[antigen]] (most reliable of the three tests).
*[[Enzyme linked immunosorbent assay (ELISA)|ELISA technique]]
*Total protein S [[antigen]]
*Protein S activity [[assay]] (not very reliable due to the inability to differentiate from [[factor V Leiden|factor V Leiden mutation]]; [[resistance]] to activated protein C).
* To read more about the diagnosis [[Protein S deficiency#Diagnosis|click here]].
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |
*[[Asymptomatic]] [[patients]] with no history of [[venous thromboembolism|venous thromboembolic events]] do not require [[medical therapy]].
*An acute event of [[venous thrombosis]] requires the same initial medical therapy regardless of the cause being [[hereditary]] or not.
*To read about the management of [[patients]] of [[pulmonary embolism]], [[Pulmonary embolism treatment approach|click here]].
*To read about the management of [[patients]] of [[deep venous thrombosis]], [[Deep vein thrombosis treatment approach|click here]].
*[[Patient]]s with [[protein S deficiency]] suffering from a [[venous thromboembolism|venous thromboembolic event]] are advised to continue [[anticoagulation]] indefinitely especially for unprovoked events (occurred without a preceding major risk event like [[surgery]], [[trauma]], [[birth control|oral contraceptives]], and [[immobility]]).
* To read more about the treatment [[Protein S deficiency#Treatment|click here]].
|-
|}


== Do's ==
== Dos ==
*A study by Wahlberg et al. demonstrated that the [[patient]]'s perception of his/her own bleeding may be understated or exaggerated, so labs vital in the assessment of bleeding disorders.<ref name="pmid7432180">{{cite journal |vauthors=Wahlberg T, Blombäck M, Hall P, Axelsson G |title=Application of indicators, predictors and diagnostic indices in coagulation disorders. I. Evaluation of a self-administered questionnaire with binary questions |journal=Methods Inf Med |volume=19 |issue=4 |pages=194–200 |date=October 1980 |pmid=7432180 |doi= |url=}}</ref>
*A study by Wahlberg et al. demonstrated that the [[patient]]'s perception of his/her own bleeding may be understated or exaggerated, so labs are vital in the assessment of bleeding disorders.<ref name="pmid7432180">{{cite journal |vauthors=Wahlberg T, Blombäck M, Hall P, Axelsson G |title=Application of indicators, predictors and diagnostic indices in coagulation disorders. I. Evaluation of a self-administered questionnaire with binary questions |journal=Methods Inf Med |volume=19 |issue=4 |pages=194–200 |date=October 1980 |pmid=7432180 |doi= |url=}}</ref>
* The initial clinical impression based on the baseline screening tests should direct specialized laboratory tests to save the time, effort and money.<ref>{{cite book | last = Bick | first = Rodger | title = Disorders of thrombosis and hemostasis : clinical and laboratory practice | publisher = Lippincott Williams & Wilkins | location = Philadelphia | year = 2002 | isbn = 978-0397516902 }}</ref>
* The initial clinical impression based on the baseline screening tests should direct specialized laboratory tests to save time, effort and money.<ref>{{cite book | last = Bick | first = Rodger | title = Disorders of thrombosis and hemostasis : clinical and laboratory practice | publisher = Lippincott Williams & Wilkins | location = Philadelphia | year = 2002 | isbn = 978-0397516902 }}</ref>


== Don'ts ==
== Don'ts ==
* It is important to not miss the [[genetic]] workup for a diagnosed [[bleeding]] disorder.
* A [[bleeding]] [[disorder]] may present as [[anemia]] so common signs/ complaints should not be missed.


==References==
==References==
Line 148: Line 281:
[[Category:Medicine]]
[[Category:Medicine]]
[[Category:Resident survival guide]]
[[Category:Resident survival guide]]
[[Category:Up-To-Date]]

Latest revision as of 19:23, 29 January 2021

Bleeding disorder
Resident Survival Guide
Overview
Causes
Diagnosis
Management
Dos
Don'ts


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Javaria Anwer M.D.[2]
Synonyms and keywords: Approach to bleeding diathesis, Bleeding diathesis workup, Bleeding diathesis management

Overview

A bleeding disorder can be due to coagulopathy, platelet dysfunction, or vessel pathology. They can be genetic or acquired. History of the site, duration, associated symptoms, and a thorough physical exam to evaluate the type of bleeding (subcutaneous vs deep tissue) are essential to diagnosis. Screening tests include CBC with peripheral blood smear, platelet count, PT, aPTT, PFA-100. Management depends upon the type of disorder, severity, and active bleeding. Plasma exchange, fresh frozen plasma, and factor replacement are the main treatment options available. The initial clinical impression based on the baseline screening tests should direct specialized laboratory tests to save time, effort, and money.

Causes

Common causes of bleeding (bleeding disorders) are enlisted below.[1][2][3][4]

 
 
 
 
 
 
 
Causes of bleeding disorders
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Platelet disorders
 
 
Coagulopathy
 
 
 
Vessel/ Supporting tissue defect
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acquired
 
Genetic
 
 
 
 
 
 
 
❑Aging
Corticosteroid use
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myeloproliferative disorders

Uremia
❑ Drugs (NSAIDs, asprin, clopidogrel, etc.)
Neoplasia
❑ Monoclonal gammopathies
DIC
Ehrlichiosis
❑ Retroviral infection
❑ Snake venom

Cirrhosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Genetic
 
 
Acquired
 
Prothrombotic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Prohemorrhagic liver diseases

Vitamin K deficiency
❑ Drug-induced such as warfarin and heparin
❑ Hemodilution and massive transfusion
Disseminated Intravascular Coagulation (DIC)
Immunoglobulin mediated Factor Deficiency (VIII, V, XIII, X)
Hyperfibrinolysis

Venom induced
 
 
 
 
 
 
 
 
 
Hemorrhagic disorders
 
 
 
Hypercoaguable disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Factor VIII deficiency (Hemophilia A)

Factor IX Deficiency (Hemophilia B)
Von Willebrand factor deficiency
Factor XI deficiency (Hemophilia C)
❑ Factor II, V, VII, X deficiency (Common Pathway Proteins)

Factor XIII deficiency and fibrinogen deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Diagnosis

The algorithm illustrates the approach to the diagnosis of bleeding disorder.[1][5][6][7][8]
Abbreviations: HEENT: Head, Eyes, Ears. Nose, and Throat exam; CBC: Complete blood count; APTT Partial thromboplastin time; CMP: Comprehensive metabolic panel; LFTs:Liver function tests
Boxes in red signify that an urgent management is needed.

 
 
 
 
 
 
 
 
 
History

Demographics: Patient age, gender,and race to screen for inherited disorders.
Bleeding history:

❑ Onset of bleed: Differentiate between spontaneous vs post-trauma or post-surgery bleed. Post-trauma may suggest an inherited bleeding disorder.
❑ Duration of bleed: Lifelong vs recent. coagulation factor defect.
❑ Type and site of bleed (skin or muscle): Petechiae, purpura, epistaxis, gingival bleeding, and bruises may suggest a vascular or platelet abnormality. Joint or muscle bleed may suggest coagulation factor abnormality.

Past medical history: For the underlying disease. History of blood or blood components transfusion. Childhood history of epistaxis, bleeding post-circumcision, and umbilical stump bleeding may suggest an inherited bleeding disorder.
Past surgical history: May reveal post-surgical bleed such as after a tooth extraction. History of poor wound healing. ❑ Drug history: For the drugs causing bleeding. Distinguish between drug induced thrombocytopenia and idiopathic thrombocytopenic purpura, or other forms of thrombocytopenia.
Family history: Certain bleeding disorders. Consanguineous marriage history.

Gynaecological history: Menorrhagia or hematuria may suggest vascular or platelet abnormality.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam

Appearance of the patient
Petechie, bruises, or hemorrhages

Vital signs: Temperature; heart rate (tachycardia with regular pulse may demonstrate hypovolemia); respiratory rate, blood pressure (hypotension); and oxygen saturation may be low due to anemia.
❑ Assess the sites and severity of the bleeding.
❑ Assess if the bleeding is due to systemic disorder, local defect, or hemostatic disorder; inherited or acquired; platelet abnormality, coagulation disorder, or vascular defect. ❑ HEENT
Cardiovascular examination
Respiratory examination
Gastrointestinal system exam includes oral examination, abdominal examination, and digital rectal exam.
Extremities exam

❑ Skin exam: Evaluate for petechie, bruises, hemorrhages. Location, symmetry, and pattern are important.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Labs

CBC with differential
Platelet count
Prothrombin time (PT)
APTT
Peripheral smear
Thrombin time

Bleeding time/ PFA-100
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Soft tissue hematoma, deep internal hemorrhage, hemarthrosis
 
 
 
 
 
 
 
 
 
 
Superficial cutaneous or mucous membrane bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PT normal, aPTT prolonged
 
PT prolonged, aPTT normal
 
 
PT prolonged, aPTT prolonged
 
 
Low platelet count
 
 
 
 
Normal platelet count
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Check thrombin time
 
 
Idiopathic Thrombocytopenic Purpura (ITP)
❑ Hereditary platelet disorder
Bone marrow failure
 
 
 
 
Check PFA-100
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prolonged
 
Normal
 
 
 
 
 
Prolonged closure time
 
 
Normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fibrinogen deficiency
Liver disease
Heparin
 
Factor II, factor V, factor X deficiency
Vitamin K deficiency
Liver disease
 
 
 
Full blood count

vWF screen

Platelet function testing
 
 
High clinical suspician
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
vWF screen
Platelet function testing (required to exclude abnormal platelet function)
 
 

Management

The following tables illustrate the treatment to common bleeding disorders.[9][10][11][12][13][14][15][16][17][18]

Disorder Labs Treatment
Factor VII deficiency
  • Measure factor VII coagulant activity for isolated prolonged PT
  • Diagnosis is confirmed with a repeat factor VII assay
  • Consider the type (such as type I: quantitative defects, type II: qualitative defects, for the management.
  • Replacement therapy: Recombinant FVIIa (rFVIIa) is most used. Median dosage of 60 μg/kg is safe for bleeding such as hematomas, hemarthrosis, and epistaxis.
Hemophilia A and Hemophilia B
Factor X deficiency
Hemophilia C
Von Willebrand disease
Microangiopathic hemolytic anemia
Glanzmann's thrombasthenia
Bernard-Soulier syndrome
Thrombocytopenia of pregnancy
SLE
Liver disease
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency

Dos

  • A study by Wahlberg et al. demonstrated that the patient's perception of his/her own bleeding may be understated or exaggerated, so labs are vital in the assessment of bleeding disorders.[20]
  • The initial clinical impression based on the baseline screening tests should direct specialized laboratory tests to save time, effort and money.[21]

Don'ts

References

  1. 1.0 1.1 Bashawri LA, Ahmed MA (May 2007). "The approach to a patient with a bleeding disorder: for the primary care physician". J Family Community Med. 14 (2): 53–8. PMC 3410146. PMID 23012146.
  2. George JN (April 2000). "Platelets". Lancet. 355 (9214): 1531–9. doi:10.1016/S0140-6736(00)02175-9. PMID 10801186.
  3. Al-Fawaz IM, Gader AM, Bahakim HM, Al-Mohareb F, Al-Momen AK, Harakati MS (May 1996). "Hereditary bleeding disorders in Riyadh, Saudi Arabia". Ann Saudi Med. 16 (3): 257–61. doi:10.5144/0256-4947.1996.257. PMID 17372424.
  4. Bick, Rodger (2002). Disorders of thrombosis and hemostasis : clinical and laboratory practice. Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0397516902.
  5. Hayward CP (2005). "Diagnosis and management of mild bleeding disorders". Hematology Am Soc Hematol Educ Program: 423–8. doi:10.1182/asheducation-2005.1.423. PMID 16304414.
  6. Blanchette VS, Sparling C, Turner C (April 1991). "Inherited bleeding disorders". Baillieres Clin Haematol. 4 (2): 291–332. doi:10.1016/s0950-3536(05)80162-3. PMID 1912663.
  7. Favaloro, Emmanuel J. (2002). "Clinical application of the PFA-100®". Current Opinion in Hematology. 9 (5): 407–415. doi:10.1097/00062752-200209000-00004. ISSN 1065-6251.
  8. Harrison, Paul (2005). "The role of PFA-100R testing in the investigation and management of haemostatic defects in children and adults". British Journal of Haematology. 130 (1): 3–10. doi:10.1111/j.1365-2141.2005.05511.x. ISSN 0007-1048.
  9. Powell JS (April 2009). "Recombinant factor VIII in the management of hemophilia A: current use and future promise". Ther Clin Risk Manag. 5 (2): 391–402. doi:10.2147/tcrm.s4412. PMC 2697540. PMID 19536318.
  10. Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, De Robertis E, Filipescu DC, Fries D, Görlinger K, Haas T, Imberger G, Jacob M, Lancé M, Llau J, Mallett S, Meier J, Rahe-Meyer N, Samama CM, Smith A, Solomon C, Van der Linden P, Wikkelsø AJ, Wouters P, Wyffels P (June 2013). "Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology". Eur J Anaesthesiol. 30 (6): 270–382. doi:10.1097/EJA.0b013e32835f4d5b. PMID 23656742.
  11. Gopinath R, Sreekanth Y, Yadav M (September 2014). "Approach to bleeding patient". Indian J Anaesth. 58 (5): 596–602. doi:10.4103/0019-5049.144664. PMC 4260306. PMID 25535422.
  12. Meeks SL, Batsuli G (December 2016). "Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches". Hematology Am Soc Hematol Educ Program. 2016 (1): 657–662. doi:10.1182/asheducation-2016.1.657. PMC 6142469. PMID 27913543.
  13. Napolitano M, Siragusa S, Mariani G (March 2017). "Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy". J Clin Med. 6 (4). doi:10.3390/jcm6040038. PMC 5406770. PMID 28350321.
  14. Hayward CP, Pai M, Liu Y, Moffat KA, Seecharan J, Webert KE, Cook RJ, Heddle NM (April 2009). "Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments". J Thromb Haemost. 7 (4): 676–84. doi:10.1111/j.1538-7836.2009.03273.x. PMID 19143930.
  15. Uprichard, James; Perry, David J. (2002). "Factor X deficiency". Blood Reviews. 16 (2): 97–110. doi:10.1054/blre.2002.0191. ISSN 0268-960X.
  16. Bertina RM, Broekmans AW, Krommenhoek-van Es C, van Wijngaarden A (February 1984). "The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency". Thromb. Haemost. 51 (1): 1–5. PMID 6547008.
  17. Faioni EM, Franchi F, Asti D, Sacchi E, Bernardi F, Mannucci PM (1993). "Resistance to activated protein C in nine thrombophilic families: interference in a protein S functional assay". Thromb Haemost. 70 (6): 1067–71. PMID 8165605.
  18. Brown, D. L.; Kouides, P. A. (2008). "Diagnosis and treatment of inherited factor X deficiency". Haemophilia. 14 (6): 1176–1182. doi:10.1111/j.1365-2516.2008.01856.x. ISSN 1351-8216.
  19. Zauber NP, Stark MW (May 1986). "Successful warfarin anticoagulation despite protein C deficiency and a history of warfarin necrosis". Ann. Intern. Med. 104 (5): 659–60. PMID 3754407.
  20. Wahlberg T, Blombäck M, Hall P, Axelsson G (October 1980). "Application of indicators, predictors and diagnostic indices in coagulation disorders. I. Evaluation of a self-administered questionnaire with binary questions". Methods Inf Med. 19 (4): 194–200. PMID 7432180.
  21. Bick, Rodger (2002). Disorders of thrombosis and hemostasis : clinical and laboratory practice. Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0397516902.