Diagnostic Challenges in Acquired Hemophilia A with Concomitant Oral Anticoagulant Use: A Case Series Analysis

Introduction Acquired hemophilia A (AHA) is an uncommon autoimmune bleeding disorder caused by inhibitory autoantibodies directed against coagulation factor VIII (FVIII). Laboratory monitoring of AHA involves serial inhibitor assays to assess treatment response and detect relapse [ 1 ]. The Bethesda assay and its Nijmegen-modified variant quantify residual FVIII activity after incubation of normal plasma with patient plasma, using either a one-stage clotting assay (OSCA) or a chromogenic substrate assay (CSA) [ 2 ]. Both assay formats, however, are susceptible to analytical interference by direct oral anticoagulants (DOACs). In particular, undetected direct factor Xa inhibitors (DFXaIs) may lead to falsely elevated Bethesda titers, potentially misinterpreted as persistent FVIII inhibitors despite clinical remission [ 3 ]. Method Two elderly female patients, aged 86 and 87 years, both with previously treated AHA and confirmed eradication of FVIII autoantibodies, presented during routine follow-up with borderline positive Nijmegen-modified Bethesda assay results (0.7 and 0.8 BU/mL; reference