血友病B患者接受人凝血酶原复合物按需治疗后四种凝血因子体内回收率的观察

In vivo recovery of coagulation factorsⅡ,Ⅶ,ⅨandⅩin hemophiliac B patients receiving prothrombin complex concentrates infusion

目的评价人凝血酶原复合物(PCC)治疗出血发作的血友病B(HB)患者中凝血因子(F)Ⅱ、Ⅶ、Ⅸ和Ⅹ的增量和体内回收率(IVR),以验证PCC中上述因子的含量,为HB治疗提供依据。方法选取2016年10月至2017年6月期间在中国医学科学院北京协和医学院北京协和医院等医疗机构参加临床试验的急性关节出血中重度HB患者,根据严重程度首次静脉注射20~40 U/kg PCC,在PCC输注前、输注后15 min采集静脉血,采用一期法测定FⅡ、FⅦ、FⅨ、FⅩ活性,计算4种凝血因子IVR;采用四点评分量表评价PCC的临床效果。结果共有69例男性患者纳入本研究,中位年龄为33岁(年龄范围为18~65岁);PCC输注剂量平均为(22.1±2.4)U/Kg,FⅡ、FⅦ、FⅨ、FⅩ的IVR分别为(1.77±0.52)、(1.63±0.85)、(1.82±0.52)、(1.80±0.61)(U/dL)/(U/kg);输注后8 h,反应优良(ER)率+良好(GR)率为88.4%(优良45例+良好16例);在输注后72 h升至100%(优良47例+良好22例);未观察到包括动静脉血栓、溶血、过敏反应和产生凝血因子抑制物等严重不良反应。结论该PCC为四因子PCC,IVR高,是一种治疗HB安全、有效的药物。

Objective To evaluate the in vivo recovery(IVR)of coagulation factors(F)Ⅱ,Ⅶ,ⅨandⅩ,and the effica⁃cy and safety of a four-factor prothrombin complex concentrate(PCC)in treating hemophilia B(HB)patients.Methods Pa⁃tients with moderate or severe HB with minor hemorrhage and enrolled in a multiple-center,open-label PCC clinical trial in Peking Union Medical College Hospital during October 2016 to June 2017 were given intravenous injection of 20-40 U/kg PCC for the treatment.Blood samples were obtained before and 15 min after PCC infusion,to determine the immediate IVRs of FⅡ,FⅦ,FⅨ,FⅩ.Clinical responses were recorded.Results Sixty-nine male patients(median age 33 years,range 18-65 years)were enrolled.The average dose infused was(22.1±2.4)U/Kg,and the IVR was FⅡ(1.77±0.52),FⅦ(1.63±0.85),FⅨ(1.82±0.52),and FⅩ(1.80±0.61)U/dL per U/kg.Excellent response(ER)rate plus good response(GR)rate was 88.4%(ER 45 cases+GR 16 cases)at 8-hour and 100%(ER 47 cases+GR 22 cases)at 72-hour.No severe adverse events(SAE)including venous or arterial thrombosis,hemolysis,allergic reactions,and inhibitor to 4 factors were reported.Conclusion This studied PCC was safe and effective for HB.The high IVR of the four factors made this PCC a potential role in other indications.