血友病A患者药代动力学参数初步评估与个体化康复训练临床疗效评价

关键词：血友病A  药代动力学  变异系数  膝关节

Keywords:hemophilia A  pharmacokinetics  coefficient of variation  knee joint

摘要：

      摘要 目的：了解血友病A患者输注凝血因子Ⅷ（FVⅢ）后药代动力学（pharmacokinetic， PK）分布的差异性情况，探索个体化康复训练的临床疗效。 方法：于2021年3月—2022年5月期间纳入13例诊断为血友病A患者为研究对象，通过myPKFiT软件监测并计算患者输注FVⅢ后的PK参数分布特征情况，根据患者个体特征开展个体化的康复训练指导，评价康复训练后年出血次数（ABR）、年关节出血次数（AJBR）、关节健康评分（HJHS），以及功能独立性量表（FIM）评分的改善情况。 结果：血友病患者输注FVⅢ后清除率、稳态分布容积、FVⅢ半衰期的均数及95%CI依次分别为0.03（0.02—0.03）dl/h/kg、0.49（0.46—0.52）dl/kg、14.05（12.19—15.92）h，变异系数（CV）依次分别为23.93%、10.03%和21.97%。符号秩和检验结果显示myPKFiT指导康复训练后患者的ABR、AJBR、HJHS和FIM等临床症状指标评分均有显著的改善（P<0.05）。 结论：血友病患者输注凝血因子后药代动力学呈现不均匀的个体间差异性分布，开展个体化康复训练能够显著改善患者的临床症状。

Abstract:

      Abstract Objective： To investigate the variation of pharmacokinetic （PK） distribution after transfusion of coagulation factor Ⅷ. （FVⅢ.） in patients with hemophilia， and to explore the clinical application of individualized rehabilitation training. Method： Thirteen patients diagnosed with hemophilia A were enrolled from March 2021 to May 2022. The distribution characteristics of PK parameters after FVⅢ. were monitored and calculated by myPKFiT software. Individualized rehabilitation training guidance was carried out according to the individual characteristics of patients. The improvement of annual bleeding rate（ABR），annual joint bleeding rate（AJBR），Hemophilia joint health score （HJHS） and functional independence measure （FIM） score after rehabilitation training was evaluated. Result： The mean and 95% CI of clearance， steady-state distribution volume， half time were 0.03（0.02—0.03） dL/hr/kg， 0.49（0.46—0.52） dL/kg， 14.05（12.19—15.92） hours， respectively. The coefficients of variation （CV） of clearance， steady-state distribution volume， half time were 23.93%， 10.03% and 21.97%， respectively. The results of the Wilcoxon signed-rank test indicated that clinical symptoms such as ABR， AJBR， HJHS and FIM were significantly improved after rehabilitation training （P<0.05）. Conclusion： The distribution of pharmacokinetics of hemophilia patients shows an uneven distribution between individuals，and individualized rehabilitation training can further improve the joint symptom score of hemophilia patients.