药代动力学指导下儿童血友病A预防治疗的疗效观察

Efficacy of pk-tailored prophylaxis in patients with hemophilia A

目的探讨儿童血友病A患者药代动力学(PK)参数的影响因素,制定个体化预防治疗方案,观察临床疗效。方法回顾性收集成都市儿童血友病中心2019年5月—2023年11月期间73例检测PK的血友病A患者的临床资料,收集其中35例PK指导预防治疗前后规律随访1年的患者的临床资料,观察比较PK指导预防治疗前后的年关节出血率(AJBR)、关节超声评分、谷浓度、凝血因子消耗量,并进行统计学分析。结果O型血患者的凝血因子Ⅷ(FⅧ)半衰期明显短于其他血型患者,vwf活性与FⅧ半衰期呈正相关,随着年龄的增加,FⅧ半衰期显著延长。35例患儿在PK指导治疗前中位AJBR 1.0(0-7)次,平均超声评分(5.3±2.2)分;PK指导治疗1年后中位AJBR为0(0-5)次,平均超声评分(3.7±1.6)分;超声评分前后比较有统计学差异。PK指导预防治疗前患者平均凝血因子用量(2417.9±648.7)IU/(kg·年),PK指导治疗后为(3150.6±714.3)IU/(kg·年)。PK指导预防治疗后14例患者调整了治疗方案,其中7例患者增加了治疗剂量,7例患者增加了治疗频次,关节零出血患者由17例增加到25例。结论PK检测可以个体化有效的指导血友病患儿预防治疗。

Objective To investigate the effect parameters on FⅧpharmacokinetic parameters in pediatric patients with hemophilia A(HA),draw up individualized preventive treatment plans,and observe clinical efficacy.Methods Seventy-three HA patients treated in Cheng Du children Hemophilia Center from May 2019 to November 2023 were enrolled.Individualized preventive treatment was developed,and thirty-five patients who were regularly followed up 1 year,the annual joint bleeding rate(AJBR),joint ultrasound score and the trough FⅧlevel,mean annual total factor consumption were observed and compared before and after treatment.Results The FⅧhalf-life of patients with type O blood were significantly shorter than those with other blood types.vwf activity is positively correlated with FⅧhalf-life.With age increased,FⅧhalf-life were prolonged.A prophylaxis plan for thirty-five was formulated under the guidance of PK parameters.After 1 year of follow-up,the mean AJBR dropped from 1.0(0-7)to 0(0-5),and the average ultrasound score dropped from(5.3±2.2)to(3.7±1.6).Mean total factor consumption increased from(2417.9tal fa)IU/(kg.year)to(3150.6tal fa)IU/(kgg0.6t),After PK-tailored prophylaxis,14 patients adjusted the treatment plan,7 patients increased the dosage,7 patients increased infusion frequency,and the number of patients with zero AJBR increased from 17 to 25.Conclusions PK-tailored prophylaxis can optimize individualized therapy in patients with hemophilia A.