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.

中文翻译：

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血浆来源的因子VIIa和X的混合物（Byclot®）可显着改善获得性A型血友病患者血浆中离体凝血潜能的损害。

血浆衍生因子（F）VIIa和FX的组合产品（pd-FVIIa / FX;Byclot®）目前可用于在日本用抑制剂对A型和B型血友病患者进行止血治疗。但是，关于其在获得性血友病A（AHA）中的凝血作用的信息尚不多。在本研究中，我们评估了pd-FVIIa / FX对AHA中凝血潜能受损的凝血作用。将旁路试剂pd-FVIIa / FX，重组FVIIa（rFVIIa）和活化的凝血酶原复合物浓缩物（aPCC）掺入与抗FVIII单克隆抗体预孵育的正常血浆（AHA模型血浆），然后添加到AHA患者的血浆中。随后进行了组织因子和鞣花酸混合物触发的凝块波形分析（CWA）。在AHA模型中，无论表位特异性如何，pd-FVIIa / FX均以剂量依赖的方式改善了所有CWA参数，相对于rFVIIa和aPCC而言有显着改善。在最大治疗剂量下，pd-FVIIa / FX在1.6 µg / mL（相当于120 µg / kg输注）下的凝结作用超出正常范围。此外，与rFVIIa和/或aPCC相比，pd-FVIIa / FX的添加导致AHA血浆中凝结电位的改善更大。这些数据表明，pd-FVIIa / FX可以显着改善AHA中凝血功能受损，并且具有潜在的治疗作用。此外，与rFVIIa和/或aPCC相比，pd-FVIIa / FX的添加导致AHA血浆中凝结电位的改善更大。这些数据表明，pd-FVIIa / FX可以显着改善AHA中凝血功能受损，并且具有潜在的治疗作用。此外，与rFVIIa和/或aPCC相比，pd-FVIIa / FX的添加导致AHA血浆中凝结电位的改善更大。这些数据表明，pd-FVIIa / FX可以显着改善AHA中凝血功能受损，并且具有潜在的治疗作用。