In vitro evaluation of global coagulation potentials in the co‐presence of plasma‐derived factors Viia/X products (Byclot^®) and emicizumab in patients with haemophilia A and inhibitors and acquired haemophilia A: A pilot study

Letter

作者: Takami, Eisuke ; Nogami, Keiji ; Nakano, Hirotoshi ; Nakajima, Yuto

Haemophilia A (HA) is a common inherited haemorrhagic disorder that results from a deficiency or defect in the protein factor (F)VIII procoagulantAccording to the recommended guidelines of the on-demand BPA therapy with emicizumab, aPCC (1.3 IU/mL in plasma or .65 IU/mL in whole blood, corresponding to 50 IU/kg) and rFVIIa(2.2 μg/mL in plasma or 1.1 μg/mL in whole blood, corresponding to 90 μg/kg) were added to the blood samples.To assess the coagulation potential of pd-FVIIa/FX together with emicizumab, pd-FVIIa/FX (.75, 1.5 or 3.0 μg/mL; 30, 60 or 120 μg/kg as FVIIa), rFVIIa (2.2 μg/mL; 90 μg/kg) or aPCC (1.3 IU/mL; 50 IU/kg), was added to FVIII-depleted plasma spiked with emicizumab (50 μg/mL).The peak thrombin level in the presence of emicizumab with pd-FVIIa/FX at various concentrations increased dose-dependently, and their coagulation potentials maintained belowor within the normal range.The effects of BPA spiking on global haemostasis in whole blood and plasma samples from three PwHA-Inh receiving emicizumab prophylaxis.These results demonstrated that the coagulant potentials improved sufficiently in the co-presence of pd-FVIIa/FX in emicizumab-treated PwHA-Inh.The present study was performed using a small sample size.Nevertheless, we demonstrated that the concomitant use of emicizumab and pd-FVIIa/FX could be useful for managing breakthrough bleeding and surgeries in PwHA-Inh and PwAHA.

2020-06-01·International Journal of Hematology4区 · 医学

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

4区 · 医学

Article

作者: Ochi, Satoshi ; Shima, Midori ; Nogami, Keiji ; Takeyama, Masahiro

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.

100 项与乾燥濃縮人血液凝固第Ⅹ因子加活性化第Ⅶ因子相关的药物交易

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