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Diagnosing Antiphospholipid Syndrome: Overcoming DOAC-Induced Assay Challenges

Diagnosing Antiphospholipid Syndrome Overcoming DOAC Induced Assay Challenges
07/09/2025

Diagnosing antiphospholipid syndrome hinges on reliable lupus anticoagulant detection, yet direct oral anticoagulants increasingly threaten assay accuracy.

Reliable detection of lupus anticoagulant remains a central laboratory criterion for antiphospholipid syndrome, an acquired coagulation disorder that carries significant risk of thrombosis and pregnancy morbidity, as guided by the ISTH guidelines and the importance of lupus anticoagulant testing. Diagnostic algorithms in clinical hematology employ phospholipid-dependent blood clotting tests—notably activated partial thromboplastin time (aPTT) and dilute Russell's viper venom time (dRVVT)—paired with confirmatory steps to distinguish phospholipid inhibitors from factor deficiencies.

As previously noted, direct oral anticoagulants (DOACs) can artificially prolong clotting times, leading to false-positive lupus anticoagulant (LA) outcomes that undermine the specificity of antiphospholipid syndrome (APS) testing and risk unnecessary long-term anticoagulation. This phenomenon underscores a pressing need for testing protocols that can differentiate true lupus anticoagulant activity from pharmacologic interference.

This challenge compels hemostasis laboratories to adopt targeted strategies for DOAC interference, from activated charcoal adsorption and plasma dilution to the use of DOAC-insensitive reagents. Earlier reports on challenges in hemostasis laboratories illustrate how rigorous assay validation and specialized neutralization procedures, such as the use of hexagonal phase phospholipid neutralization or platelet neutralization procedures, can restore diagnostic precision.

Recent procedural updates emphasize handling anticoagulant interference by standardizing preanalytical variables—timing specimen collection at trough drug levels—and integrating DOAC-removal protocols. In one clinical scenario, a patient on rivaroxaban presented with a prolonged dRVVT ratio initially interpreted as positive for lupus anticoagulant, but repeat testing after drug clearance confirmed the absence of a phospholipid-dependent inhibitor.

Laboratories and clinical teams must embed these advances into routine workflows, maintaining vigilance for anticoagulant effects and continuously validating blood clotting tests to safeguard against diagnostic pitfalls in antiphospholipid syndrome.

Key Takeaways:
  • The role of lupus anticoagulant testing is critical in diagnosing APS amidst anticoagulant challenges.
  • Direct oral anticoagulants can induce false-positive LA results, complicating APS diagnosis.
  • Updated strategies, including DOAC-neutralization, are essential for ensuring accurate results in hemostasis laboratories.
  • Continuous adaptation in testing procedures and timing of sample collection is necessary to improve diagnostic precision.
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