How long after stopping anticoagulants, such as warfarin (International Normalized Ratio (INR) < 1.5) or direct oral anticoagulants like apixaban (Factor Xa inhibitor) or rivaroxaban (Factor Xa inhibitor), should hypercoagulable testing be ordered?

From the Guidelines

Hypercoagulable testing should be performed at least 2-4 weeks after discontinuation of anticoagulant therapy, with a minimum 2-week washout period recommended for direct oral anticoagulants (DOACs) like apixaban and rivaroxaban. For warfarin, testing should be delayed until the INR is less than 1.5 for at least two weeks, as the anticoagulant effect persists until adequate levels of proteins involved in the coagulation cascade are achieved after stopping warfarin therapy, a process that takes at least 48 to 72 hours 1. The waiting period is crucial because anticoagulants directly interfere with the laboratory assays used to detect hypercoagulable states, potentially causing false-negative or false-positive results. For example, warfarin reduces protein C and S levels, which could falsely suggest a deficiency, while Factor Xa inhibitors like apixaban and rivaroxaban can affect antithrombin assays and clot-based testing 1.

Some key points to consider when ordering hypercoagulable testing after anticoagulant therapy include:

• The half-life of the anticoagulant, such as apixaban, which is approximately 12 hours 1
• The time it takes for the anticoagulant effect to be reversed, such as warfarin, which takes at least 48 to 72 hours 1
• The potential for false-negative or false-positive results due to interference with laboratory assays
• The consideration of genetic testing for inherited thrombophilias if anticoagulation cannot be safely discontinued

In cases where anticoagulation cannot be safely discontinued, genetic testing for inherited thrombophilias (such as Factor V Leiden or Prothrombin G20210A mutations) may be considered as these are not affected by anticoagulant therapy. If testing must be performed while the patient is on anticoagulation, this should be clearly noted on the laboratory requisition, and results should be interpreted with caution.

From the Research

Hypercoagulable Testing After Anticoagulants

• The optimal timing for ordering hypercoagulable testing after stopping anticoagulants is not explicitly stated in the provided studies 2, 3, 4, 5, 6.
• However, it is known that anticoagulants such as warfarin and direct oral anticoagulants (DOACs) like apixaban and rivaroxaban affect coagulation factors and may influence the results of hypercoagulable testing.
• For warfarin, a minimum of 5 days is recommended for its effects to diminish after stopping the medication, considering its mechanism of action on vitamin K-dependent factors 2.
• For DOACs, their effects are more immediate, and their half-lives are generally shorter than warfarin's, but specific guidance on when to test after stopping these medications is not provided in the studies.
• The decision on when to order hypercoagulable testing should consider the patient's clinical condition, the reason for anticoagulation, and the specific anticoagulant used, as well as the laboratory tests' sensitivity to the effects of these medications.
• Given the lack of direct evidence, clinical judgment and consultation with relevant guidelines or experts in the field may be necessary to determine the appropriate timing for hypercoagulable testing after anticoagulant therapy has been discontinued.