In emicizumab prophylaxis, the concomitant therapy using bypassing agents (BPAs) is required for breakthrough bleeding and invasive procedures with attention to thrombotic complications. To predict coagulant effects of BPAs in emicizumab‐treated patients with haemophilia A (PwHA) with inhibitor (PwHAwI), blood samples from emicizumab‐treated PwHAwI (n = 8) and PwHA without inhibitor (n = 2) in phase 1/2 and HAVEN 1 study, spiked with activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa (rFVIIa) ex vivo, and blood samples from emicizumab‐treated PwHAwI‐receiving BPAs were analysed by Ca²⁺‐triggered rotational thromboelastometry (ROTEM) and ellagic acid/tissue factor‐triggered clot waveform analysis (CWA). Spiked aPCC, corresponded to 10–100 U/kg, markedly shortened ROTEM parameters beyond the normal range, while spiked rFVIIa, corresponded to 90–270 μg/kg, shortened them within near‐normal range. Each of the spiked BPA‐improved adjusted maximum coagulation velocity of CWA to within or near the normal range. In blood samples at post‐infusion of aPCC (44–73 U/kg) or rFVIIa (79–93 μg/kg), the parameters of both assays improved to approximately the normal range. Taken together, ex vivo results of spiking tests in ROTEM and CWA, except aPCC spiking test in ROTEM, were relatively consistent with in vivo ones, and could usefully predict the coagulant effects of concomitant bypassing therapy for emicizumab‐treated PwHAwI.

中文翻译：

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使用艾美珠单抗预防性治疗的A型血友病患者使用综合凝血测定法对绕过疗法的止血效果进行预测。

在艾米珠单抗的预防中，对于突破性出血和侵入性治疗，需要注意使用血栓并发症，因此需要使用旁路试剂（BPA）的伴随疗法。为了预测BPA在接受抑霉素（A）的血友病A（PwHA）治疗且有抑制剂（PwHAwI）的患者中的BPA的凝血作用，在1/2期中分别从经Emicizumab治疗的PwHAwI（n  = 8）和无抑制剂的PwHA（n  = 2）中采集血样HAVEN 1研究，离体掺入活化的凝血酶原复合物浓缩物（aPCC）或重组因子VIIa（rFVIIa），并用Ca ²⁺分析了接受艾米珠单抗治疗的PwHAwI接收的BPA的血样触发式旋转血栓弹性测定（ROTEM）和鞣花酸/组织因子触发的血凝波形分析（CWA）。加标的aPCC相当于10–100 U / kg，显着缩短了ROTEM参数，超出了正常范围，而加标的rFVIIa相当于90–270μg/ kg，使它们在接近正常范围内缩短了。每个加标的BPA均将CWA的最大凝固速度调整为正常范围内或附近。在aPCC（44–73 U / kg）或rFVIIa（79–93μg/ kg）输注后的血液样本中，两种测定的参数均改善到大约正常范围。两者合计，除了ROTEM中的aPCC峰值测试，ROTEM和CWA中的峰值测试的离体结果与体内相对一致 药物，可以有效预测艾米珠单抗治疗的PwHAwI伴随旁路治疗的凝血作用。