Deep vein thrombosis laboratory tests: Difference between revisions

Jump to navigation Jump to search
 
(38 intermediate revisions by 11 users not shown)
Line 1: Line 1:
'''Editors-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] '''Associate Editor-In-Chief''': [[User:Ujjwal Rastogi|Ujjwal Rastogi, MBBS]] [mailto:urastogi@perfuse.org]
__NOTOC__
{| class="infobox" style="float:right;"
|-
| [[File:Siren.gif|30px|link=Deep vein thrombosis resident survival guide]]|| <br> || <br>
| [[Deep vein thrombosis resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}
'''Editor(s)-In-Chief:''' {{ATI}}, [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com]; '''Associate Editor(s)-In-Chief:''' {{CZ}} ; [[User:Kashish Goel|Kashish Goel, M.D.]]; '''Assistant Editor(s)-In-Chief:''' [[User:Justine Cadet|Justine Cadet]]


{{Deep vein thrombosis}}
{{Deep vein thrombosis}}


==Overview==
==Overview==
Deep vein thrombosis is a common condition seen in the Emergency Department. Standard of care for diagnosis of DVT includes a combination of a clinical pre-test probability rule known as Well's criteria, D-dimer blood testing, and Radiology department ultrasound.
D-dimer is used in the diagnosis of [[deep vein thrombosis]] among patients with low or unlikely probability of [[venous thromboembolism]].<ref name="pmid16403932">{{cite journal| author=Wells PS, Owen C, Doucette S, Fergusson D, Tran H| title=Does this patient have deep vein thrombosis? | journal=JAMA | year= 2006 | volume= 295 | issue= 2 | pages= 199-207 | pmid=16403932 | doi=10.1001/jama.295.2.199 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16403932  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213132 Review in: Evid Based Med. 2006 Aug;11(4):119]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16813372 Review in: ACP J Club. 2006 Jul-Aug;145(1):24] </ref><ref name="pmid11453709">{{cite journal| author=Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D et al.| title=Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 2 | pages= 98-107 | pmid=11453709 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11453709  }} </ref>  While 500 ng/mL has long been the most commonly used cut off value for abnormal D-dimer concentration, recent studies suggest the use of an age adjusted cut-off concentration of D-dimer.  The age adjusted cut-off value of D-dimer is 500 ng/mL for subjects whose age is less than 50 years, and the age multiplied by 10 for subjects older than 50 years.<ref name="pmid22511491">{{cite journal| author=Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C et al.| title=Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. | journal=Haematologica | year= 2012 | volume= 97 | issue= 10 | pages= 1507-13 | pmid=22511491 | doi=10.3324/haematol.2011.060657 | pmc=PMC3487551 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22511491  }} </ref><ref name="pmid23645857">{{cite journal| author=Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA et al.| title=Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. | journal=BMJ | year= 2013 | volume= 346 | issue=  | pages= f2492 | pmid=23645857 | doi=10.1136/bmj.f2492 | pmc=PMC3643284 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23645857  }} </ref><ref name="pmid24643601">{{cite journal| author=Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A et al.| title=Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. | journal=JAMA | year= 2014 | volume= 311 | issue= 11 | pages= 1117-24 | pmid=24643601 | doi=10.1001/jama.2014.2135 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24643601  }} </ref>


==D-dimer==
==Laboratory Findings==
'''{{main|d-dimer}}'''
===D-Dimer===
In a low-probability situation, current practice is to commence investigations by testing for [[D-dimer]] levels.  This cross-linked [[fibrin degradation product]] is an indication that [[thrombosis]] is occurring, and that the [[blood clot]] is being dissolved by [[plasmin]].  A low D-dimer level should prompt other possible [[Deep vein thrombosis differential diagnosis|diagnoses]] (such as a ruptured [[Baker's cyst]], if the patient is at sufficiently low clinical probability of DVT.<ref name="pmid14507948">{{cite journal |author=Wells PS, Anderson DR, Rodger M, ''et al'' |title=Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis |journal=N. Engl. J. Med. |volume=349 |issue=13 |pages=1227-35 |year=2003 |pmid=14507948 |doi=10.1056/NEJMoa023153}}</ref><ref name="pmid12755550">{{cite journal |author=Bates SM, Kearon C, Crowther M, ''et al'' |title=A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis |journal=Ann. Intern. Med. |volume=138 |issue=10 |pages=787-94 |year=2003 |pmid=12755550 |doi=}}</ref>
''For a detailed discussion on D-dimer, please click '''[[D-dimer|here]]'''.''


It should be noted that latex D-dimer assays are insensitive and have no role in screening for deep vein thrombosis.
* [[D-dimer]] is a cross-linked [[fibrin degradation product]] and a marker of endogenous [[fibrinolysis]]. In the setting of ongoing thrombosis, D-dimer's concentration is elevated in the blood and thus makes it a screening tool to rule out [[DVT]].


==Other blood tests==
* D-dimer is the "test of choice" in patients who are considered to be at low or intermediate risk of DVT according to [[Wells score for DVT|pre-test probability]].  D-dimer is more useful if its negative rather than positive. It has a great '''negative predictive value''' in low to moderate risk patients.  If D-dimer is elevated, then [[DVT]] should be confirmed with [[Deep vein thrombosis ultrasound|ultrasound]].<ref name="pmid14507948">{{cite journal |author=Wells PS, Anderson DR, Rodger M, ''et al'' |title=Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis |journal=N. Engl. J. Med. |volume=349 |issue=13 |pages=1227-35 |year=2003 |pmid=14507948 |doi=10.1056/NEJMoa023153}}</ref><ref name="pmid12755550">{{cite journal |author=Bates SM, Kearon C, Crowther M, ''et al'' |title=A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis |journal=Ann. Intern. Med. |volume=138 |issue=10 |pages=787-94 |year=2003 |pmid=12755550 |doi=}}</ref>
Other blood tests usually performed at this point are:
 
* [[complete blood count]]
* The cut off value for abnormal D-dimer concentration is 500 ng/mL.  Interpretation of D-dimer may be improved by using age adjusted levels:<ref name="pmid22511491">{{cite journal| author=Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C et al.| title=Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. | journal=Haematologica | year= 2012 | volume= 97 | issue= 10 | pages= 1507-13 | pmid=22511491 | doi=10.3324/haematol.2011.060657 | pmc=PMC3487551 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22511491  }} </ref><ref name="pmid23645857">{{cite journal| author=Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA et al.| title=Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. | journal=BMJ | year= 2013 | volume= 346 | issue=  | pages= f2492 | pmid=23645857 | doi=10.1136/bmj.f2492 | pmc=PMC3643284 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23645857 }} </ref><ref name="pmid24643601">{{cite journal| author=Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A et al.| title=Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. | journal=JAMA | year= 2014 | volume= 311 | issue= 11 | pages= 1117-24 | pmid=24643601 | doi=10.1001/jama.2014.2135 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24643601  }} </ref>
* Primary [[coagulation]] studies: [[prothrombin time|PT]], [[APTT]], [[Fibrinogen]]
** Patients less than 50 years old: normal D-dimer is less than 500 µg/L
* [[liver enzyme]]s
** In patients 50 years or older: normal D-dimer is adjusted to be age multiplied by 10
* [[renal function]] and [[electrolyte]]s
 
* [[prostate specific antigen]] measurement in men over the age of 50.
====Specificity and Sensitivity====
==Test==
A large number of D-dimer assays are available and may vary in-between hospitals. In a meta-analysis of 217 studies involving [[DVT]] patients, the sensitivities of the D-dimer enzyme-linked immunofluorescence assay (ELFA) (96%), micro plate [[enzyme-linked immunosorbent assay]] (94%), and latex quantitative assay (93%; PE 95%) were superior to the whole-blood [[D-dimer]] assay (83%), and latex qualitative assay (69%). Because of this, [[ELISA]] assays are termed as "highly sensitive" and whole blood D-dimer assays is "moderately sensitive".
*[[Homan's test]]: is said to be present when passive dorsiflexion of the ankle by the examiner elicits sharp pain in the calf.. A '''positive Homans''' sign does not positively diagnose DVT (poor positive predictive value), and a'''negative Homans''' sign does not rule out the DVT diagnosis (poor negative predictive value).
Thus, D-dimer has a high sensitivity (sNOUT) and low specificity (sPIN) for [[DVT]]. This means that D-dimer is a better test for "ruling out" [[DVT]] rather than "ruling in".
*Pratt's sign: Squeezing of posterior calf elicits pain
 
However, these [[medical sign]]s do not perform well and are not included in [[clinical prediction rule]]s that combine best findings in order to diagnose DVT.<ref name="pmid16403932">{{cite journal| author=Wells PS, Owen C, Doucette S, Fergusson D, Tran H| title=Does this patient have deep vein thrombosis? | journal=JAMA | year= 2006 |volume= 295 | issue= 2 | pages= 199-207 | pmid=16403932 | doi=10.1001/jama.295.2.199 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16403932 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16813372 Review in: ACP J Club. 2006 Jul-Aug;145(1):24[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213132 Review in: Evid Based Med. 2006 Aug;11(4):119] </ref>
====D-dimer Elevation in Other Conditions====
D-dimer can be elevated in following conditions, which should be kept in mind while assessing this biomarker in patients with suspected [[DVT]]:
* Malignancy
* [[Disseminated intravascular coagulation]]
* Elderly
* [[Infection]]
* [[Pregnancy]]
* [[Surgery]]/[[Trauma]]
* Inflammatory conditions
* [[Atrial fibrillation]]
* [[Stroke]]
 
=== Workup for Hypercoagulation ===
*Workup for [[hypercoagulation]] includes:
**Activated [[protein C]] resistance
**[[Factor V Leiden]] mutation
**[[Protein C]]
**[[Protein S]] (free and total)
**[[Antithrombin]]
**[[Lupus anticoagulant]]
**[[Anticardiolipin antibodies]]
**Plasma [[homocysteine]] values
 
* The hypercoagulability tests are not part of the routine workup for all patients with DVT. The hypercoagulability workup should be considered in the case of unprovoked venous thrombosis at an early age (< 40 years), strong family history of more than 2 relative who had VTE symptoms, and pregnant women who had a previous VTE episode in the absence of a significant trigger.<ref name="pmid20128794">{{cite journal| author=Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S et al.| title=Clinical guidelines for testing for heritable thrombophilia. | journal=Br J Haematol | year= 2010 | volume= 149 | issue= 2 | pages= 209-20 | pmid=20128794 | doi=10.1111/j.1365-2141.2009.08022.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20128794  }} </ref>
 
* The hypercoagulability workup should not be performed in the cases of:<ref name="pmid20128794">{{cite journal| author=Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S et al.| title=Clinical guidelines for testing for heritable thrombophilia. | journal=Br J Haematol | year= 2010 | volume= 149 | issue= 2 | pages= 209-20 | pmid=20128794 | doi=10.1111/j.1365-2141.2009.08022.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20128794  }} </ref>
** Upper limb thrombosis
** [[Central venous catheter]] related thrombosis
** [[Retinal vein]] occlusion
** Recent major [[surgery]]
** Recent [[trauma]]
** Recent immobilization
** Active [[cancer]]


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


[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Pulmonology]]
[[Category:Angiology]]
[[Category:Cardiology]]
[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Mature chapter]]
[[Category:Vascular surgery]]
[[Category:Up-To-Date]]
[[Category:Cardiovascular diseases]]


{{WH}}
{{WH}}
{{WS}}
{{WS}}

Latest revision as of 15:09, 17 July 2014



Resident
Survival
Guide

Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] ; Kashish Goel, M.D.; Assistant Editor(s)-In-Chief: Justine Cadet

Deep Vein Thrombosis Microchapters

Home

Patient Information

Overview

Classification

Pathophysiology

Causes

Differentiating Deep vein thrombosis from other Diseases

Epidemiology and Demographics

Risk Factors

Triggers

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Approach

Assessment of Clinical Probability and Risk Scores

Assessment of Probability of Subsequent VTE and Risk Scores

History and Symptoms

Physical Examination

Laboratory Findings

Ultrasound

Venography

CT

MRI

Other Imaging Findings

Treatment

Treatment Approach

Medical Therapy

IVC Filter

Invasive Therapy

Surgery

Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Special Scenario

Upper extremity DVT

Recurrence

Pregnancy

Trials

Landmark Trials

Case Studies

Case #1

Deep vein thrombosis laboratory tests On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Deep vein thrombosis laboratory tests

CDC on Deep vein thrombosis laboratory tests

Deep vein thrombosis laboratory tests in the news

Blogs on Deep vein thrombosis laboratory tests

Directions to Hospitals Treating Deep vein thrombosis

Risk calculators and risk factors for Deep vein thrombosis laboratory tests

Overview

D-dimer is used in the diagnosis of deep vein thrombosis among patients with low or unlikely probability of venous thromboembolism.[1][2] While 500 ng/mL has long been the most commonly used cut off value for abnormal D-dimer concentration, recent studies suggest the use of an age adjusted cut-off concentration of D-dimer. The age adjusted cut-off value of D-dimer is 500 ng/mL for subjects whose age is less than 50 years, and the age multiplied by 10 for subjects older than 50 years.[3][4][5]

Laboratory Findings

D-Dimer

For a detailed discussion on D-dimer, please click here.

  • D-dimer is the "test of choice" in patients who are considered to be at low or intermediate risk of DVT according to pre-test probability. D-dimer is more useful if its negative rather than positive. It has a great negative predictive value in low to moderate risk patients. If D-dimer is elevated, then DVT should be confirmed with ultrasound.[6][7]
  • The cut off value for abnormal D-dimer concentration is 500 ng/mL. Interpretation of D-dimer may be improved by using age adjusted levels:[3][4][5]
    • Patients less than 50 years old: normal D-dimer is less than 500 µg/L
    • In patients 50 years or older: normal D-dimer is adjusted to be age multiplied by 10

Specificity and Sensitivity

A large number of D-dimer assays are available and may vary in-between hospitals. In a meta-analysis of 217 studies involving DVT patients, the sensitivities of the D-dimer enzyme-linked immunofluorescence assay (ELFA) (96%), micro plate enzyme-linked immunosorbent assay (94%), and latex quantitative assay (93%; PE 95%) were superior to the whole-blood D-dimer assay (83%), and latex qualitative assay (69%). Because of this, ELISA assays are termed as "highly sensitive" and whole blood D-dimer assays is "moderately sensitive". Thus, D-dimer has a high sensitivity (sNOUT) and low specificity (sPIN) for DVT. This means that D-dimer is a better test for "ruling out" DVT rather than "ruling in".

D-dimer Elevation in Other Conditions

D-dimer can be elevated in following conditions, which should be kept in mind while assessing this biomarker in patients with suspected DVT:

Workup for Hypercoagulation

  • The hypercoagulability tests are not part of the routine workup for all patients with DVT. The hypercoagulability workup should be considered in the case of unprovoked venous thrombosis at an early age (< 40 years), strong family history of more than 2 relative who had VTE symptoms, and pregnant women who had a previous VTE episode in the absence of a significant trigger.[8]

References

  1. Wells PS, Owen C, Doucette S, Fergusson D, Tran H (2006). "Does this patient have deep vein thrombosis?". JAMA. 295 (2): 199–207. doi:10.1001/jama.295.2.199. PMID 16403932. Review in: Evid Based Med. 2006 Aug;11(4):119 Review in: ACP J Club. 2006 Jul-Aug;145(1):24
  2. Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D; et al. (2001). "Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer". Ann Intern Med. 135 (2): 98–107. PMID 11453709.
  3. 3.0 3.1 Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C; et al. (2012). "Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded". Haematologica. 97 (10): 1507–13. doi:10.3324/haematol.2011.060657. PMC 3487551. PMID 22511491.
  4. 4.0 4.1 Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA; et al. (2013). "Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis". BMJ. 346: f2492. doi:10.1136/bmj.f2492. PMC 3643284. PMID 23645857.
  5. 5.0 5.1 Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A; et al. (2014). "Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study". JAMA. 311 (11): 1117–24. doi:10.1001/jama.2014.2135. PMID 24643601.
  6. Wells PS, Anderson DR, Rodger M; et al. (2003). "Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis". N. Engl. J. Med. 349 (13): 1227–35. doi:10.1056/NEJMoa023153. PMID 14507948.
  7. Bates SM, Kearon C, Crowther M; et al. (2003). "A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis". Ann. Intern. Med. 138 (10): 787–94. PMID 12755550.
  8. 8.0 8.1 Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S; et al. (2010). "Clinical guidelines for testing for heritable thrombophilia". Br J Haematol. 149 (2): 209–20. doi:10.1111/j.1365-2141.2009.08022.x. PMID 20128794.

Template:WH Template:WS