Abstract:
How to optimize perioperative factor VIII (FVIII) replacement through hemostatic monitoring is critically important to manage hemophilia A patients. The bispecific antibody emicizumab binds activated FIX (FIXa) and FX to functionally mimic FVIIIa. While being used for hemostatic control in hemophilia A, this therapeutic antibody inconveniently interferes with coagulation tests using human FIXa and FX, such as activated partial thromboplastin time (APTT) and FVIII activity measurement based on one-stage clotting assays. Clot waveform analysis (CWA) extends the interpretation of measurement curves for coagulation time to provide global information. We performed APTT-CWA to monitor perioperative hemostasis in a hemophilia A patient on emicizumab undergoing liver transplantation. Plasma samples were treated with anti-idiotype monoclonal antibodies against emicizumab to enable accurate coagulation assays. Kinetics of maximum coagulation velocity and acceleration mimicked that of FVIII activity. These CWA parameters better correlated with FVIII activity than APTT. The plateaus of them were observed at FVIII activity of 100% or more, supporting the protocol for perioperative FVIII replacement. Thus, CWA may measure coagulation potential in hemophilia A patients undergoing liver transplantation, aiding in optimizing perioperative hemostasis.
摘要:
如何通过止血监测优化围手术期因子VIII(FVIII)的替代对于治疗血友病A患者至关重要。双特异性抗体艾咪珠单抗结合活化的FIX(FIXa)和FX以在功能上模拟FVIIIa。在用于血友病A的止血控制时,这种治疗性抗体不方便地干扰使用人FIXa和FX的凝血测试,如活化部分凝血活酶时间(APTT)和基于一阶段凝血试验的FVIII活性测量。凝块波形分析(CWA)扩展了凝血时间测量曲线的解释,以提供全局信息。我们进行了APTT-CWA,以监测接受肝移植的埃米珠单抗治疗的血友病A患者的围手术期止血。用抗独特型单克隆抗体对血浆样品进行处理以实现准确的凝血测定。最大凝血速度和加速度的动力学模拟FVIII活性。与APTT相比,这些CWA参数与FVIII活性更好地相关。在100%或更高的FVIII活性下观察到它们的平台,支持围手术期FVIII置换方案.因此,CWA可以测量接受肝移植的血友病A患者的凝血电位,帮助优化围手术期止血。