445 Hemophilia A: when the bleeding patient looks worse than lab testing would indicate

Introduction/Objective Patients who develop bleeding out of proportion to factor activity levels should have laboratory techniques reviewed. Methods/Case Report A 22-year-old male with mild hemophilia A on on-demand recombinant Factor VIII (rFVIII) therapy presented with worsening hematoma. Childhood genotyping demonstrated 1820G>A Arg531His mutation. Historical Factor VIII (FVIII) activity ranged from 10-20% at diagnosis. Subsequent levels ranged 39-43% without clear explanation. The patient initially suffered a spontaneous adductor muscle hematoma requiring rFVIII infusions. FVIII activity was 51% pre-infusion, 128% post-infusion, and 74% 24-hours post-infusion. Ten days later, his hematoma enlarged. Pre-infusion FVIII activity failed due to specimen instability. Repeat level after rFVIII infusion was 51% by one-stage assay (OSA). Repeat FVIII activity checked by OSA and chromogenic substrate assay (CSA) concurrently during rFVIII infusion were 53% and 17% respectively. After infusion, levels were 83% and 55%. While the patient’s mutation is associated with mild phenotype, his FVIII activity by OSA was incongruent with his worsening hematoma. This mutation has been reported to demonstrate discrepant FVIII activity by OSA and CSA, with CSA more consistent with clinical phenotype. Results NA Conclusion The OSA is the default assay at most institutions. For patients with hemophilia and significant bleeding despite reassuring FVIII activity, it is important to consider assay performance in addition to excluding other bleeding disorders. Accurate results guide treatment and rFVIII dosing. Depending on the mutation, either CSA or OSA may reflect clinical phenotype.