Clinical settings and anticoagulants that may interfere with testing for thrombophilia

Thrombophilic disorder	Clinical settings and anticoagulants
Thrombophilic disorder	Acute thrombosis	Heparin therapy	Warfarin	Direct oral anticoagulants*
Factor V Leiden	NC	NC	NC	NC
Prothrombin G20210A	NC	NC	NC	NC
Protein C (PC) deficiency	NC	NC	Cannot measure^¶	Cannot measure using functional assays^Δ
Protein S (PS) deficiency	Can be lowered^◊	NC	Cannot measure^¶	Cannot measure using functional assays^Δ
Antithrombin (AT) deficiency	Can be lowered^◊	Lowered	NC	Cannot measure using functional assyas^Δ
Antiphospholipid antibodies	NC	NC	NC	NC
Lupus anticoagulant^§	NC	Cannot measure^Δ	False positives possible	Cannot measure^Δ
Increased factor VIII activity	Acute phase reactant. Do not test while inflammation is still present.
Acquired AT deficiency:
Neonatal period; pregnancy; liver disease; DIC; nephrotic syndrome; major surgery; acute thrombosis; treatment with L-asparaginase, heparin, or estrogens
Acquired protein C deficiency:
Neonatal period; liver disease; vitamin K deficiency; DIC, chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil; inflammation; treatment with warfarin or L-asparaginase
Acquired protein S deficiency:
Neonatal period; pregnancy; liver disease; vitamin K deficiency; DIC; treatment with warfarin, L-asparaginase, or estrogens

Refer to UpToDate topics on the specific hypercoagulable disorders for additional information. If a result is abnormal in a patient receiving an anticoagulant, it may be prudent to repeat the test in the absence of the anticoagulant, if possible.

NC: not changed; LMW heparin: low molecular weight heparin; AT: antithrombin; DIC: disseminated intravascular coagulation.
* Direct oral anticoagulants (DOACs) include dabigatran, apixaban, edoxaban, and rivaroxaban.
¶ If it is important to test for these deficiencies while the patient is still anticoagulated, switch the treatment to full-dose heparin or LMW heparin and discontinue warfarin for at least 2 weeks before measurement. Comparing protein S or C levels with prothrombin antigen in stably anticoagulated patients is not reliable, as accurate measurement of prothrombin antigen levels is a research assay that is not generally available.
Δ Some laboratories can perform testing if they use a reagent to inactivate or remove the anticoagulant (heparinase for heparin, activated charcoal for DOACs). Some functional assays for protein C, protein S, and AT deficiency are not subject to interference by DOACs.
◊ Results for protein S and AT can be affected by acute thrombosis; it is most cost effective to avoid testing during the initial presentation. However, if plasma levels are well within the normal range at presentation, deficiency is essentially excluded.
§ Lupus anticoagulant testing should only be done in the absence of any anticoagulant, as it is a clot-based test. However, antiphospholipid antibodies can be tested because they are serologic assays and are unaffected by anticoagulation.

Graphic 76966 Version 12.0

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Clinical settings and anticoagulants that may interfere with testing for thrombophilia