Deep vein thrombosis laboratory tests
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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 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.
- 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:
- 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.[8]
- The hypercoagulability workup should not be performed in the cases of:[8]
- Upper limb thrombosis
- Central venous catheter related thrombosis
- Retinal vein occlusion
- Recent major surgery
- Recent trauma
- Recent immobilization
- Active cancer
References
- ↑ 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
- ↑ 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.
- ↑ 3.0 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.
- ↑ 4.0 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.
- ↑ 5.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 8.0 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.