Plasma-derived factors VIIa and X mixtures (Byclot®) significantly improve impairment of coagulant potential ex vivo in plasmas from acquired hemophilia A patients.
A combined product of plasma-derived factor (F)VIIa and FX (pd-FVIIa/FX; Byclot®) is currently available for the hemostatic treatment of hemophilia A and B patients with inhibitors in Japan. Limited information is available, however, on its coagulant effect in acquired hemophilia A (AHA). In the present study, we assessed the coagulant effect of pd-FVIIa/FX on impairment of coagulation potentials in AHA. The bypassing agents, pd-FVIIa/FX, recombinant FVIIa (rFVIIa), and activated prothrombin complex concentrates (aPCC) were spiked with normal plasma preincubated with anti-FVIII monoclonal antibody (AHA-model plasma), and added to plasmas from AHA patients. Clot waveform analysis (CWA) triggered by the mixture of tissue factor and ellagic acid was subsequently performed. In the AHA-model, pd-FVIIa/FX improved all of the CWA parameters in a dose-dependent manner, irrespective of epitope specificity, with significant improvements relative to rFVIIa and aPCC. The coagulant effect of pd-FVIIa/FX at 1.6 µg/mL (corresponding to 120 µg/kg infusion) at the maximum therapeutic dose was outside the normal range. Moreover, the addition of pd-FVIIa/FX led to a greater improvement in the coagulant potentials in AHA plasmas than those of rFVIIa and/or aPCC. These data suggest that pd-FVIIa/FX significantly improves the impaired coagulant potentials in AHA and is potentially therapeutic.
['Ochi|Satoshi|S|', 'Takeyama|Masahiro|M|http://orcid.org/0000-0002-9348-9815', 'Shima|Midori|M|', 'Nogami|Keiji|K|']
D001777:Blood Coagulation D003029:Coagulants D004305:Dose-Response Relationship, Drug D004338:Drug Combinations D015942:Factor VIIa D005170:Factor X D006467:Hemophilia A D006801:Humans D066298:In Vitro Techniques
Acquired hemophilia A Inhibitor Bypassing agent Clot waveform analysis Plasma-derived FVIIa/FX