How to perform a hypercoagulable workup on patients taking direct oral anticoagulants (DOACs) such as apixaban (eliquis), rivaroxaban (xarelto), or dabigatran (pradaxa)?

Performing a Hypercoagulable Workup in Patients on DOACs

To properly evaluate patients for hypercoagulable states while on direct oral anticoagulants (DOACs), the anticoagulant should be temporarily discontinued for at least 48 hours before testing to avoid interference with test results.

Effect of DOACs on Hypercoagulable Testing

DOACs significantly interfere with most hypercoagulable workup tests, making interpretation challenging or impossible:

Factor Xa Inhibitors (Apixaban, Rivaroxaban, Edoxaban)

• Direct impact on:
  • Anti-Xa activity assays
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT) - variable effect
  • Lupus anticoagulant testing
  • Protein C and S activity assays
  • Antithrombin activity assays

Direct Thrombin Inhibitors (Dabigatran)

• Direct impact on:
  • Thrombin time (TT)
  • aPTT
  • Lupus anticoagulant testing
  • Protein C and S activity assays
  • Antithrombin activity assays

Recommended Protocol for Hypercoagulable Testing

1. Timing of DOAC Discontinuation:

   • Apixaban/Rivaroxaban/Edoxaban: Discontinue for at least 48 hours
   • Dabigatran: Discontinue for at least 48-72 hours (longer with renal impairment)

2. Confirming DOAC Clearance:

   • For Factor Xa inhibitors: Anti-Xa activity test should be negative
   • For Dabigatran: Thrombin time or dilute thrombin time should be normal

3. Bridging Considerations:

   • For high thrombotic risk patients, consider bridging with LMWH during testing
   • Stop LMWH 24 hours before blood collection

4. Tests to Include in Workup:

   • Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein)
   • Factor V Leiden mutation
   • Prothrombin gene mutation
   • Protein C, protein S, and antithrombin levels
   • Homocysteine levels
   • JAK2 mutation (if polycythemia or unusual site thrombosis)

5. Special Considerations:

   • Genetic tests (Factor V Leiden, prothrombin gene mutation) are not affected by DOACs and can be performed without discontinuation
   • Antiphospholipid antibody testing requires DOAC discontinuation to avoid false positives

Managing Patients During Testing

1. Risk Assessment:

   • Evaluate thrombotic risk vs. bleeding risk
   • Consider patient's history, indication for anticoagulation, and time since last thrombotic event

2. For High Thrombotic Risk Patients:

   • Use prophylactic or therapeutic LMWH bridging during DOAC interruption
   • Stop LMWH 24 hours before blood collection
   • Resume DOAC after testing is complete

3. For Lower Thrombotic Risk Patients:

   • Simple discontinuation of DOAC without bridging may be appropriate
   • Resume DOAC promptly after testing

Common Pitfalls to Avoid

• Inadequate DOAC washout: Testing too soon after DOAC discontinuation leads to false results
• Failure to confirm DOAC clearance: Always verify drug absence before interpreting results
• Inappropriate bridging: Overlapping LMWH and DOACs increases bleeding risk
• Overlooking renal function: Patients with impaired renal function need longer DOAC washout periods
• Misinterpreting results: Even with proper discontinuation, some tests may show residual effects

Laboratory Communication

Always communicate with the laboratory about:

• The specific DOAC the patient is taking
• When the last dose was administered
• Whether confirmatory testing for DOAC absence should be performed

By following these protocols, clinicians can obtain reliable hypercoagulable testing results while minimizing thrombotic risk during the necessary DOAC interruption period.