国产静注人免疫球蛋白制品中残留活化凝血因子Ⅺ活性检测  

Activated coagulation factor Ⅺ(FⅪa) activity in intravenous immunoglobulin preparations from China: An analysis test

作　　者：管利东[1] 侯书婷 马秋平[1] 王威[1] GUAN Lidong;HOU Shuting;MA Qiuping;WANG Wei(.1.National Institutes for Food and Drug Control,Beijing 100050,China School of Life Science,Peking University)

机构地区：[1]中国食品药品检定研究院,北京100050 [2]北京大学生命科学学院

出　　处：《中国输血杂志》2021年第5期505-509,共5页Chinese Journal of Blood Transfusion

基　　金：国家药典委员会药品标准制修订研究课题(2018S018)。

摘　　要：目的了解国产静注人免疫球蛋白制品(IVIG)中凝血因子Ⅺ(FⅪ)的活性水平,为提高我国IVIG制品的安全性及开展质量控制提供参考依据。方法利用显色底物法、凝固法,分析国内23个厂家(品牌)共71批次(其中半数为近效期)的IVIG送检制品的活化凝血因子Ⅺ(FⅪa)、FⅪ和非活化的部分凝血活酶时间(NAPTT)。结果 FⅪa活性(mIU/mL):15个厂家(品牌)的32批次IVIG为<0.1或定量限(0.02),12个厂家24批次IVIG为0.1~1(0.39±0.20),余下6个厂家15批次IVIG为1~47(13.27±15.61)。FⅪ活性(mIU/mL):21个厂家58批次低于检测限(10)未检出,其余6个厂家13批次IVIG为13~309(69.0±98.1),其FⅪa活性>1mIU/mL。NAPTT(s):6个厂家15批次IVIG为>150,NAPTT比值0.67~0.94(0.83±0.07),其中7个批次为≤0.8。结论国产不同品牌的IVIG制品中FⅪa和FⅪ活性存在较大差异,多数品牌IVIG制品的FⅪa和FⅪ活性较低。IVIG生产企业应加强对其生产工艺的验证和评估以及制品促凝活性的监测,以消除血栓形成风险。Objective To investigate the activity level of coagulation factor Ⅺ(FⅪ) in IVIG products, which would provide support for improving the safety and quality control of IVIG products in China. Methods A total of 71 batches of IVIG products(half of which were closed to expiry date) from 23 domestic manufacturers(brands) were submitted for inspection and assayed for procoagulant activity including FⅪa, FⅪ and NAPTT activity with a chromogenic assay, coagulation proenzymes levels using one stage clotting assays and non-activated partial thromboplastin time(NAPTT). Results FⅪa(mIU/mL):32 lots of IVIGs from 15 manufacturers(brands) possessed activities below 0.1 or the detection limit of the assays, 24 IVIG lots from 12 manufacturers were between 0.1~1(0.39±0.20),the remaining 15 IVIG lots from 6 manufacturers had FⅪa activity greater than 1 up to 47(13.27±15.61). FⅪ(mIU/mL):there were no detectable activities of FⅪ in 58 lots from 21 manufacturers, the other 13 lots from 6 manufacturers had IVIGs between 13~309(69.0±98.1),which included in 15 lots of IVIG whose FⅪa activity were greater than 1 mIU/mL. NAPTT(s):The coagulation times for aforementioned 15 IVIG lots were all above 150 s in the NAPTT test. The NAPTT ratios varied between 0.67 and 0.94(0.83±0.07), and 7 of 15 IVIGs had NAPTT ratios below or equal to 0.8. Conclusion There are substantial differences in the FⅪ and FⅪa activities in the IVIG preparations from 23 different manufacturers. Most of them had a lower activities;certain lots from specific manufacturers had relatively higher FⅪa activities. Manufactures should evaluate the manufacturing processes and monitor IVIG preparations for the presence of factor Ⅺ-like activity in case of thrombotic risks.

关 键 词：静注人免疫球蛋白 活化的凝血因子Ⅺ FⅪ活性 风险评估 

分 类 号：R446.1[医药卫生—诊断学] R392.33[医药卫生—临床医学]