What is the approach to a hypercoagulability workup in a patient on Eliquis (apixaban)?

Hypercoagulability Workup in Patients on Apixaban (Eliquis)

For patients on apixaban (Eliquis) requiring hypercoagulability testing, laboratory evaluation should be delayed until the patient has been off the medication for at least 48 hours to avoid false results and misinterpretation.

Impact of Apixaban on Coagulation Testing

Apixaban significantly affects several coagulation tests that are critical for hypercoagulability workup:

• Direct interference with Factor Xa-based assays: As a direct Factor Xa inhibitor, apixaban will invalidate any test that measures Factor Xa activity
• Falsely elevated INR/PT: Though less affected than with warfarin, results may still be unreliable
• Minimal effect on aPTT: Generally less affected but still potentially misleading
• Falsely low protein C and S activity levels: These tests often rely on Factor Xa-dependent pathways

Recommended Protocol for Testing

Timing of Testing

1. Discontinue apixaban: Stop medication at least 48 hours before testing 1

   • For patients with renal impairment, consider longer washout (72+ hours)
   • Note that apixaban has a half-life of 12 hours in most patients

2. Risk assessment: Before stopping anticoagulation, evaluate thrombotic risk

   • For high-risk patients (recent thrombosis, mechanical heart valves), consider bridging with heparin
   • Heparin can be discontinued 4-6 hours before blood collection

Essential Tests to Include

Once apixaban has been appropriately discontinued, the following tests should be ordered:

• Basic coagulation panel:

  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT)
  • Complete blood count with platelets

• First-line thrombophilia testing:

  • Factor V Leiden mutation
  • Prothrombin gene mutation (G20210A)
  • Protein C activity
  • Protein S activity
  • Antithrombin III activity
  • Lupus anticoagulant
  • Anticardiolipin antibodies
  • Beta-2 glycoprotein antibodies 2

• Additional testing (based on clinical suspicion):

  • Homocysteine levels
  • Factor VIII activity
  • JAK2 mutation (if myeloproliferative disorder suspected)
  • Paroxysmal nocturnal hemoglobinuria (PNH) screen

Special Considerations

Acute Thrombosis Situations

For patients with acute thrombosis who cannot safely discontinue anticoagulation:

• Collect genetic tests (Factor V Leiden, prothrombin mutation) as these are not affected by anticoagulants
• Consider delaying functional assays until stable enough to temporarily discontinue apixaban
• Document timing of sample collection relative to last apixaban dose

Restarting Anticoagulation

• Resume apixaban as soon as testing is complete
• For patients at high thrombotic risk, consider bridging with heparin until apixaban reaches therapeutic levels
• Standard dosing can be resumed without titration 1

Common Pitfalls to Avoid

1. Testing while still on apixaban: This is the most common error and leads to unreliable results and misdiagnosis

2. Inadequate washout period: Not allowing sufficient time for drug clearance, especially in patients with renal impairment

3. Inappropriate test selection: Ordering tests that are known to be affected by Factor Xa inhibitors even after discontinuation

4. Failure to consider timing of testing: Certain conditions (acute thrombosis, inflammation, pregnancy) can affect test results independent of anticoagulation

5. Misinterpreting borderline results: Values near the reference range cutoff should be interpreted with caution and potentially repeated

By following this structured approach to hypercoagulability testing in patients on apixaban, clinicians can obtain reliable results that accurately guide diagnosis and management decisions while minimizing thrombotic risk during the testing period.