血友病A患儿凝血因子Ⅷ抑制物相关临床研究  

Clinical study on factorⅧinhibitor in children with hemophilia A

作　　者：商保军[1,2] 杨世伟 雷平冲[3,4] 马荣军 何向东 袁晓莉 姜丽 李玉龙 董晓燕 王臻[3] 张琳 朱尊民[1,2] Shang Baojun;Yang Shiwei;Lei Pingchong;Ma Rongjun;He Xiangdong;Yuan Xiaoli;Jiang Li;Li Yulong;Dong Xiaoyan;Wang Zhen;Zhang Lin;Zhu Zunmin(Institute of Hematology of Henan Provincial People’s Hospital,450003,China;Henan Key laboratory of Stem Cell Differentiation and Modification,Zhengzhou 450003,China;Department of Hematology,Henan Provincial People's Hospital/People’s Hospital of Zhengzhou University,Zhengzhou 450003,China;Henan Provincial Registration Management Center of Hemophilia,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院血液病研究所,郑州450003 [2]河南省干细胞分化与调控重点实验室,郑州450003 [3]河南省人民医院(郑州大学人民医院)血液科,郑州450003 [4]河南省血友病登记管理中心,郑州450003

出　　处：《中华血液学杂志》2020年第2期138-142,共5页Chinese Journal of Hematology

基　　金：诺和诺德基金会中国项目第8期(2017-2020)。

摘　　要：目的探讨血友病A(HA)患儿凝血因子Ⅷ(FⅧ)抑制物产生的相关因素及抑制物产生前后出血与关节病表现的差异。方法对2015年1月至2018年8月河南省血友病管理中心登记收治的381例16岁以下HA患儿进行回顾性分析。结果381例HA患儿中,轻型116例(30.4%),中间型196例(51.4%),重型69例(18.1%)。FⅧ抑制物阳性患者54例(14.2%),高滴度、低滴度分别为22、32例。血友病家族史与FⅧ抑制物阳性相关[P<0.001,OR=3.299(95%CI 1.743~5.983)];高强度暴露与FⅧ抑制物的产生相关[P=0.002,OR=2.587(95%CI 1.414~4.731)]。高强度暴露与高滴度FⅧ抑制物产生相关[P=0.001,OR=8.689(95%CI 2.464~30.638)]。54例HA患者产生抑制物后,总体关节年出血率、创伤性年出血率增加(z=-3.440,P=0.001;z=-2.232,P=0.026),而非关节年出血率、自发性年出血率与抑制物产生前比较差异无统计学意义(z=-1.342,P=0.180;z=-1.414,P=0.157)。关节超声评分较产生抑制物前差异无统计学意义(z=-0.632,P=0.527)。结论血友病家族史、高强度暴露可增加HA患儿发生FⅧ抑制物的风险,且高强度暴露可增加HA患者出现高滴度抑制物的风险。Objective To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A(HA).Methods Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018.Results A total of the 381 children were enrolled with 116(30.4%)mild,196(51.4%)moderate,and 69(18.1%)severe cases;54 patients(14.2%)had inhibitors,including 22 high and 32 low titer inhibitors.Positive family history was positively associated with inhibitors[P<0.001,OR=3.299(95%CI 1.743-5.983)],and high-intensity exposure was associated with inhibitors[P=0.002,OR=2.587(95%CI 1.414-4.731)].High-intensity exposure was associated with high titer inhibitor production[P=0.001,OR=8.689(95%CI 2.464-30.638)],and high-intensity exposure increased the risk of high titer inhibitors in HA patients.After inhibitors occurred in 54 patients with HA,the rates of overall joint annual bleeding(z=-3.440,P=0.001)and traumatic annual bleeding(z=-2.232,P=0.026)increased,but the rates of the annual joint bleeding(z=-1.342,P=0.180)and spontaneous annual bleeding(z=-1.414,P=0.157)remained to be not statistically significant.The joint ultrasound score did not change significantly after the inhibitor information(z=-0.632,P=0.527).Conclusions Positive family history and highintensity exposure could increase the risk of FⅧinhibitors in HA patients,and high-intensity exposure increased the risk of high titer inhibitors.The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.

关 键 词：血友病A 抑制物 超声评分 血友病性关节病 

分 类 号：R725.5[医药卫生—儿科]