Emicizumab Improves Ex Vivo Clotting Function in Patients with Mild/Moderate Hemophilia A
Emicizumab Improves Ex Vivo Clotting Function in Patients with Mild/Moderate Hemophilia A
复制标题
DOI：
10.1055/s-0040-1710315
复制
发表时间：
2020-06-01
影响因子：
6.7
通讯作者：
Shima, Midori
中科院分区：
文献类型：
--
作者：
Nakajima, Yuto;Nogami, Keiji;Shima, Midori
背景：Emicizumab预防是一种很有前途的治疗方法，可以减少严重感染的A型血友病患者(PwHA)的出血事件。预计埃米珠单抗对轻/中度PwHA(PwMHA)也有类似的效果，尽管这种作用尚未被研究。目的我们评估了Eicizumabin PwMHA的体外凝血作用。方法利用凝血酶原时间/激活的部分凝血酶原时间混合试剂触发的凝块波形分析(CWA)来检测Emiizumabin(F)VIII缺陷血浆与重组(R)FVIII混合的凝血作用以及16例PwMHA的天然血浆。使用了CWA参数-|min1|(Ad|min1|)。结果加入不同浓度的rFVIII后，血浆中不同浓度rFVIII的Ad|min1|与Delta Ad|min1|呈负相关，并以此作为标准参考值。加入埃米珠单抗后，16例PwMHA的AD|min1|(4.57+/-0.50)分别增加到5.05+/-0.54和5.37+/-0.60，但仍低于正常范围(7.22+/-0.21)。与rFVIII确定的参考值相比，Delta Ad|min1|水平在5例中高1.5至2倍，在4例中低0.4至0.6倍。在某些情况下，基因分析表明，这些发现可能是特定的点突变造成的。然而，使用rFVIII突变体的进一步研究表明，Delta Ad|min1|的差异与个体FVIII基因缺陷无关。结论Emicizumab增强了PwMHA的凝血能力。评估埃米珠单抗的体外凝血活性可能有助于在治疗前预测这些患者的凝血潜力。
Background Emicizumab prophylaxis is a promising treatment that reduces bleeding events in severely affected patients with hemophilia A (PwHA). It is anticipated that emicizumab could be similarly effective in mild/moderate PwHA (PwMHA) although this effect has not been investigated.Aim We evaluated ex vivo coagulant effects of emicizumabin PwMHA.Methods Clot waveform analysis (CWA) triggered by prothrombin time/activated partial prothrombin time-mixed reagents was utilized to examine coagulant effects of emicizumabin factor (F)VIII-deficient plasma mixed with recombinant (r)FVIIIand in native plasmas from 16 PwMHA. The CWA parameter, adjusted-|min1| (Ad|min1|), was used. Increases in Ad|min1| (Delta Ad|min1|) mediated by emicizumab were calculated from the slopes of regression lines in the presence of rFVIII.Results Ad|min1| in FVIII-deficient plasma with various concentrations of rFVIII negatively correlated with Delta Ad|min1|by adding emicizumab, and these data were defined as standard reference values. Ad|min1| (4.57 +/- 0.50) in 16 PwMHA increased to 5.05 +/- 0.54 and 5.37 +/- 0.60 by adding emicizumab at 50 and 100 mu g/mL, respectively, but remained lower than the normal range (7.22 +/- 0.21). Delta Ad|min1| levels were 1.5 to 2-fold higher in five cases and 0.4 to 0.6-fold lower in four cases, compared with reference values determined by rFVIII. In some cases, genetic analyses suggested that specific point mutations could have contributed to these findings. Further studies using rFVIII mutants indicated, however, that the differences in Delta Ad|min1| were not related to individual FVIII gene defects.Conclusion Emicizumab enhances coagulation potential in PwMHA. Assessment of ex vivo coagulant activity of emicizumab could be helpful for predicting coagulant potentials prior to treatment in these patients.