艾美赛珠单抗对血友病A凝血试验检测的影响  

Effect of emicizumab on coagulation assays of hemophila A

作　　者：陈振萍 李刚 李泽坤 甄英姿 黄昆 吴润晖 CHEN Zhenping;LI Gang;LI Zekun;ZHEN Yingzi;HUANG Kun;WU Runhui(Hematology Oncology Center,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,Beijing Key Laboratory of Pediatric Hematology Oncology,National Key Discipline of Pediatrics,Capital Medical University,Key Laboratory of Major Diseases in Children,Ministry of Education,Beijing,100045,China)

机构地区：[1]国家儿童医学中心,首都医科大学附属北京儿童医院血液肿瘤中心,儿童血液病与肿瘤分子分型北京市重点实验室,儿科学国家重点学科,儿科重大疾病研究教育部重点实验室,北京100045

出　　处：《临床血液学杂志》2020年第6期771-775,共5页Journal of Clinical Hematology

基　　金：首都卫生发展科研专项项目(No:首发2018-2-2094);北京市科委首都临床特色应用研究(No:Z181100001718182)。

摘　　要：目的:评估艾美赛珠单抗对不同方法的凝血实验室检测结果的影响,为艾美赛珠单抗治疗的血友病A儿童患者提供适当的中国儿童实验室监测数据。方法:纳入2019年8月—2020年9月就诊于我院血友病门诊接受艾美赛珠单抗治疗的血友病A患儿11例,采集枸橼酸钠抗凝的外周血共16份,进行凝血试验检测,包括活化部分凝血活酶时间(APTT),一期法FⅧ活性(FⅧ︰C)检测,发色底物法FⅧ︰C(包括人源和牛源两种FⅧ︰C检测试剂盒)及基于3种FⅧ检测方法的Nijmegen改良法检测FⅧ抑制物。结果:使用艾美赛珠单抗的血浆样本APTT值为(24.63±1.71)s,较使用前的APTT值显著缩短。应用一期法测得的FⅧ︰C水平为(479.1%±110.3%),牛源FⅧ︰C检测试剂盒发色底物法检测的FⅧ︰C水平与基线水平一致,均<1%,人源FⅧ︰C试剂盒发色底物法检测的FⅧ︰C水平为(18.97%±7.78%)。基于一期法和人源FⅧ︰C试剂盒发色底物法检测的抑制物检测结果均为阴性,而基于牛源FⅧ︰C试剂盒检测的FⅧ数据计算的抑制物结果显示7份样本阳性,9份样本阴性。结论:APTT和一期法FⅧ︰C检测试验受艾美赛珠单抗药物的影响,无法反映体内真正的凝血水平。人源性FⅧ发色底物法检测试剂对艾美赛珠单抗敏感,可用于该药在体内凝血能力的评估,但不可用于FⅧ抑制物的检测。牛源性FⅧ发色底物法检测试剂对艾美赛珠单抗不敏感,可反映体内真正的FⅧ︰C水平,适用于FⅧ抑制物的检测。Objective:To evaluate the effect of emicizumab on the coagulation laboratory tests and to provide appropriate monitoring data for Chinese children with hemophilia A treated with emicizumab.Method:Eleven hemophilia A receiving emicizumab in our hemophilia clinic were enrolled from August 2019 to September 2020.Total 16 anticoagulant peripheral blood samples of sodium citrate were collected for coagulation tests,including activated partial thromboplastin time(APTT),one-stage FⅧ assay,chromogenic substrate FⅧ assays(human FⅧ︰C kit and bovine FⅧ︰C kit)and FⅧ inhibitors detection based on three FⅧ︰C assays.Result:The APTT value of plasma samples with emicizumab was(24.63±1.71)s,which was significantly shorter than that of plasmas without emicizumab.The level of FⅧ︰C detected by one-stage assay was(479.1%±110.3%).The level of FⅧ activity detected by bovine FⅧ︰C detection kit was consistent with the baseline level(all<1%).The level of FⅧ activity detected by human FⅧ︰C kit chromogenic substrate method was(18.97%±7.78%).All FⅧ inhibitors were negative based on chromogenic substrate assay or one-stage FⅧ︰C.The results of bovine FⅧ︰C chromogenic substrate assay showed that 7 cases were positive and 9 cases were negative,which was consistent with the results before treatment.Conclusion:APTT and one-stage FⅧ assays are affected by emicizumab and could not reflect the real coagulation activity in vivo.The human FⅧ chromogenic substrate assay is sensitive to emicizumab and can be used to evaluate the clotting ability of emicizumab in vivo,but it is not recommended for the detection of FⅧ inhibitor.The bovine FⅧ chromogenic substrate assay is not sensitive to emicizumab and can reflect the realFⅧ︰C in vivo,which is suitable for the detection of FⅧ inhibitor.

关 键 词：艾美赛珠单抗 血友病A 活化部分凝血活酶时间 FⅧ活性检测 一期法 发色底物法 

分 类 号：R554.1[医药卫生—血液循环系统疾病]