How to perform thrombophilia testing in patients on Novel Oral Anticoagulants (NOACs)?

Thrombophilia Testing in Patients on Novel Oral Anticoagulants (NOACs)

Thrombophilia testing in patients on NOACs requires temporary discontinuation of the anticoagulant prior to testing to avoid false results, with specific timing based on the NOAC type and renal function. 1, 2

Impact of NOACs on Thrombophilia Tests

• NOACs significantly interfere with thrombophilia screening tests, causing both false-positive and false-negative results that can lead to misdiagnosis 1, 2
• Direct thrombin inhibitors (dabigatran) affect thrombin-based assays, while factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) interfere with factor Xa-based tests 2
• Lupus anticoagulant testing is particularly susceptible to interference, with up to 75% false-positive results in patients on NOACs 1
• Protein C, protein S, and antithrombin activity assays based on clotting methods are affected, while antigenic/chromogenic methods show less interference 2

Recommended Approach for Thrombophilia Testing

Timing of NOAC Discontinuation

• For patients with normal renal function:

  • Discontinue rivaroxaban, apixaban, or edoxaban at least 24 hours before blood collection 2
  • Discontinue dabigatran at least 48 hours before blood collection due to its longer half-life in patients with normal renal function 3

• For patients with impaired renal function:

  • Extend the discontinuation period based on creatinine clearance 3
  • For severe renal impairment (CrCl <30 mL/min), discontinue NOACs at least 48-72 hours before testing 3

Laboratory Considerations

• Inform the laboratory about NOAC use when ordering thrombophilia tests 3
• Consider using specialized adsorbent procedures like DOAC-Stop® to remove NOAC interference when immediate testing is necessary 1
• Document the exact time of last NOAC dose relative to blood sampling 3
• Consider specific assays to confirm complete clearance of the NOAC:
  • Diluted thrombin time or ecarin clotting time for dabigatran 3
  • Anti-Xa activity assays for factor Xa inhibitors 3

Risk Management During Testing

• Assess patient's thrombotic risk using validated tools (e.g., CHA₂DS₂-VASc score for AF patients) 3
• For high-risk patients (CHA₂DS₂-VASc ≥3), consider bridging with low molecular weight heparin during NOAC interruption 3
• Resume NOAC therapy as soon as possible after sample collection 3
• In patients with very high thrombotic risk where anticoagulation cannot be interrupted, consider:
  • Using chromogenic or immunologic assays that are less affected by NOACs 2
  • Interpreting results with caution, acknowledging potential interference 2

Special Considerations

• Patients with severe thrombophilia (protein C/S deficiency, antithrombin deficiency, homozygous factor V Leiden) may have higher recurrence risk during anticoagulation interruption 4
• Adherence to the exact timing of NOAC discontinuation is crucial for accurate test results 4
• Consider the clinical urgency of thrombophilia testing versus the risk of temporary anticoagulation interruption 3
• For patients with recent thrombosis (<3 months), postpone thrombophilia testing if possible until stable anticoagulation can be established 3

Pitfalls to Avoid

• Do not rely on routine coagulation tests (PT/INR, aPTT) to determine if NOAC effect has cleared, as they have poor sensitivity 5
• Avoid thrombophilia testing during acute thrombotic events as results may be affected regardless of NOAC presence 3
• Do not interpret thrombophilia test results without knowledge of the timing of last NOAC dose 3
• Remember that even after recommended discontinuation periods, some patients may still have residual NOAC activity due to individual pharmacokinetic variations 5