What is the false-positive rate of antiphospholipid syndrome (APS) antibodies in patients on direct oral anticoagulants (DOACs)?

False-Positive Rate of Antiphospholipid Syndrome Antibodies in Patients on Direct Oral Anticoagulants

Direct oral anticoagulants (DOACs) can significantly interfere with lupus anticoagulant (LA) testing, causing false-positive results, though the exact percentage varies depending on the specific test methodology used.

Interference of DOACs with Antiphospholipid Antibody Testing

Lupus Anticoagulant Testing

• DOACs can cause both false-positive and false-negative LA test results, making testing during anticoagulation generally discouraged 1
• The interference occurs primarily with clotting-based assays (dRVVT and APTT) which are the standard tests for LA detection
• Even low DOAC levels can affect LA testing results, with no guarantee of lack of interference even at trough levels 1

Specific Effects on Testing Components:

1. Screening tests: DOACs prolong clotting times in screening tests
2. Mixing tests: Can be affected in both directions
3. Confirmatory tests: May show incomplete correction

Strategies to Mitigate DOAC Interference:

DOAC Removal Approaches

• Commercial DOAC removal agents can be used prior to testing 1
• Activated charcoal is an inexpensive alternative but may have more heterogeneous effects 1
• Important considerations with removal agents:
  • Sample pretreatment might influence clotting times
  • DOAC removal may be incomplete
  • Comparing pre/post-removal results is recommended
  • Minor changes in LA assay results after adding removal agents can alter interpretation in both directions (negative to positive and vice versa) 1

Alternative Testing Approaches

• Sampling during the trough period of DOAC administration (though this doesn't guarantee lack of interference) 1
• Using Taipan snake venom time/ecarin time (TSVT/ET) assays which show less interference with anti-Xa DOACs 1

Clinical Implications and Recommendations

Testing Recommendations

• Ideally, testing should be done before anticoagulation is started 2
• If testing must be done while on DOACs:
  1. Use DOAC removal agents when available
  2. Compare results before and after DOAC removal
  3. Consider TSVT/ET assays as an alternative test
  4. Interpret results with caution, especially if around cutoff values

Risk of Misdiagnosis

• False-positive LA results can lead to misdiagnosis of APS
• This is particularly concerning as DOACs are contraindicated in triple-positive APS (positive for lupus anticoagulant, anticardiolipin, and anti-beta 2-glycoprotein I antibodies) 3, 4
• Both rivaroxaban and dabigatran FDA labels specifically warn against use in triple-positive APS due to increased thrombotic risk compared to vitamin K antagonists 3, 4

Solid Phase Assays

• Unlike LA testing, anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) are measured with immunologic solid phase assays that are not affected by DOACs 1
• These tests should be preferred when evaluating for APS in patients on DOACs

Conclusion

While the exact percentage of false-positive LA tests in patients on DOACs is not precisely quantified in the literature, the interference is significant enough that the International Society on Thrombosis and Haemostasis (ISTH) recommends against LA testing during anticoagulation when possible 1. When testing is unavoidable, DOAC removal agents should be used, though they may not completely eliminate interference. Solid phase assays for other antiphospholipid antibodies are not affected by DOACs and should be prioritized in the diagnostic workup.