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Plasma-derived factors VIIa and X mixtures (Byclot®) significantly improve impairment of coagulant potential ex vivo in plasmas from acquired hemophilia A patients

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Abstract

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.

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Acknowledgements

This study was supported by the research grant from KM Biologics Co., Ltd.

Author information

SO: performed experiments, analyzed data, and made the figures, MT: designed the research, performed experiments, analyzed data, interpreted the data, and wrote the paper, MS: supervised this study, and KN: designed the research, interpreted the data, and wrote and edited the manuscript.

Correspondence to Masahiro Takeyama.

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Conflict of interest

TM, MS, and KN receive research support from KM Biologics, Novo Nordisk, and Takeda. TM, KN, and MS receive (consulting) honoraria from these companies. SO has no conflict of interest to declare.

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Ochi, S., Takeyama, M., Shima, M. et al. Plasma-derived factors VIIa and X mixtures (Byclot®) significantly improve impairment of coagulant potential ex vivo in plasmas from acquired hemophilia A patients. Int J Hematol (2020). https://doi.org/10.1007/s12185-020-02837-6

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Keywords

  • Acquired hemophilia A
  • Plasma-derived FVIIa/FX
  • Clot waveform analysis
  • Bypassing agent
  • Inhibitor