5例儿童A型血友病合并凝血因子Ⅷ抑制物生成临床回顾性分析  

Clinical Retrospective Analysis of 5 Children with Hemophilia A Complicated with Recombinant FactorⅧInhibitor Formation

作　　者：易维佳 郭玉霞[1] 曾星 屈泽欣 肖剑文[1] Yi Weijia;Guo Yuxia;Zeng Xing;Qu Zexin;Xiao Jianwen(Children’s Hospital of Chongqing Medical University,Chongqing Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院,儿童发育疾病研究教育部重点实验室,国家儿童健康与疾病临床医学研究中心,儿童发育重大疾病国家国际科技合作基地,重庆400014

出　　处：《儿科药学杂志》2022年第10期37-41,共5页Journal of Pediatric Pharmacy

摘　　要：目的:通过回顾性分析5例血友病A(HA)合并凝血因子Ⅷ(FⅧ)抑制物生成的病例资料,以指导制定HA治疗方案。方法:回顾性分析5例HA合并FⅧ抑制物临床特征,采用聚合酶链式反应(PCR)技术及DNA测序分析检测血友病相关基因突变情况。结果:5例患儿均为男性,均于外院接受基因重组FⅧ按需治疗。5例均进行患儿及母亲HA基因检查,为母亲遗传所致。发现抑制物时中位年龄24个月。出血停止后5例均不愿诱导免疫耐受治疗。病例1小剂量艾美赛珠单抗预防,病例3及病例4接受四因子凝血酶原复合物按需治疗,病例2继续第三代基因重组FⅧ标准预防,病例5第三代基因重组FⅧ低剂量预防治疗。随访至2021年1月,随访时间(7.60±1.75)月,3例高滴度患儿抑制物仍>5 BU/mL,2例患儿抑制物已恢复正常。结论:重型HA患儿接受FⅧ治疗后均可能出现抑制物,抑制物的产生与遗传及治疗因素均有密切关系。HA伴抑制物患儿发生出血事件后,应根据患儿出血情况、家庭具体情况尽可能选择恰当的止血方案,降低残疾及死亡风险。Objective:To retrospectively analyze the clinical data of 5 cases of hemophilia A(HA)complicated with recombinant factorⅧ(FⅧ)inhibitor formation,so as to guide the treatment of HA.Methods:The clinical characteristics of 5 cases of HA complicated with FⅧinhibitor formation were retrospectively analyzed,and the mutation of hemophilia-related genes was detected by polymerase chain reaction(PCR)technology and DNA sequencing analysis.Results:All of the 5 patients were male and received gene FⅧon-demand treatment in other hospitals.Five cases were tested for HA genes in the children and mothers,and all were due to maternal inheritance.The median age at inhibitor discovery was 24 months.Five cases were unwilling to induce immune tolerance therapy after the bleeding was stopped.Case 1 received low-dose emecizumab prophylaxis,case 3 and 4 received on-demand treatment with four-factor prothrombin complex concentrate,case 2 continued standard prophylaxis with third-generation recombinant FⅧ,and case 5 received low-dose prophylaxis with third-generation recombinant FⅧ.The follow-up period was(7.60±1.75)months until Jan.2021.The inhibitor in 3 children with high titer was still>5 BU/mL,and the inhibitor in 2 children had returned to normal state.Conclusion:Inhibitors may occur in children with severe HA treated with FⅧ,and the production of inhibitor is closely related to both genetic and therapeutic factors.After bleeding events in HA children with inhibitor,the appropriate hemostatic scheme should be selected as far as possible according to the bleeding situation of the child and the specific situation of the family,so as to reduce the risk of disability and death.

关 键 词：血友病A 抑制物生成 治疗 艾美赛珠单抗 

分 类 号：R725.5[医药卫生—儿科]