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Thrombophilia Testing – Reliable on Anticoagulants?

Stephan Moll, MD writes…  The decision how long to treat a patient with venous thromboembolism (VTE) with anticoagulants can often be made based on the patient’s history alone, i.e. the circumstances of the VTE event (provoked versus unprovoked).  Often, no thrombophilia testing is needed.  However, if one were to do thrombophilia testing, what is the right time to test? It is important to realize that some anticoagulants can influence test results.

 

Testing on Warfarin

  • Reliable/accurate:
    • Genetic testing for factor V Leiden and the prothrombin 20210 (= factor II) mutation is reliable.
    • Anticardiolipin antibody and anti-beta-2-glycoprotein-I antibody testing is accurate.
    • Antithrombin tests are usually reliable on warfarin, except in few individuals, in whom warfarin may lead to a slight increase in antithrombin values. In addition, antithrombin values are often transiently low at the time of a thrombotic event and while on heparin or low molecular weight heparin.
    • D-dimer: The test result on warfarin is accurate. And a positive D-dimer on warfarin predicts a higher risk of recurrent VTE if the patient comes off warfarin, a negative D-dimer a lower risk [example: ref. 1; HERDOO-2 score]. However, if the D-dimer is used for helping make a decision on how long to treat with anticoagulants, then the D-dimer should also be tested after the patient has come off anticoagulants, such as 4 weeks later [example: ref 2.; DASH score].
  • Not reliable/not accurate:
    • Protein C and protein S tests are not reliable. Results are almost always low on warfarin. Testing should be done 3 or more weeks after having come off warfarin. Also: protein S values will be low in (a) the women who takes estrogens (birth control pill, ring or patch; hormone replacement therapy) or who is pregnant, and (b) the patient with liver disease. Values are also often transiently low at the time of an acute thrombotic event.
    • Lupus anticoagulant can be falsely positive on warfarin [ref. 3]. However, typically test results are only mildly abnormal [ref. 3]; a clearly/strikingly positive result is likely a real abnormal result.

 

Testing on Xarelto, Pradaxa, or Eliquis

  • Reliable/accurate:
    • Genetic testing for factor V Leiden and the prothrombin 20210 (=factor II) mutation is accurate.
    • Anticardiolipin antibody and anti-beta-2-glycoprotein-I antibody results are accurate.
    • Free and total protein S, protein C antigen, antithrombin antigen levels are reliable.
    • D-dimer. While test results are reliable on the new oral anticoagulants [ref. 1], the usefulness of this test as a predictor of a higher or lower risk of another clot once a patients is off blood thinners is not known.
  • Not reliable/not accurate:
    • Protein C activity and protein S activity (also called functional tests); results may appear normal, even though a patient may have a deficiency of protein C or S [ref. 4].
    • Antithrombin activity may be influenced (falsely high values) [ref. 4].
    • APC resistance assay may be falsely normal (i.e. false negative) [ref. 5].
    • Lupus anticoagulant tests: I am not aware of any publications at this point on whether the new oral anticoagulants influence lupus anticoagulant test results.

 

Conclusion

  • When ordering or interpreting thrombophilia test results in a patient on an anticoagulant, it is important to know which test results are influenced by the anticoagulant (summarizing table here).
  • If thrombophilia testing is undertaken, a number of tests are best done while not anticoagulants.

 

References

  1. Tosetto A et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost. 2012 Jun;10(6):1019-25.
  2. Rodger MA et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008; 179:417–426.
  3. Pengo V et al. Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples. J Thromb Haemost 2007;5:925–930.
  4. Adcock DM et al. The Effect of Dabigatran on Select Specialty Coagulation Assays. Am J Clin Pathol 2013;139:102-109.
  5. Johnson NV et al. Advances in laboratory testing for thrombophilia. Am. J. Hematol 2012; 87:S108–S112.

 

Last Updated:  April 22nd, 2013

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