Factor IX inhibitors in haemophilia B: A report of National Haemophilia Registry in China
作者全名："Dou, Xueqing; Zhang, Wenhui; Poon, Man-Chiu; Zhang, Xinsheng; Wu, Runhui; Feng, Xiaoqin; Yang, Linhua; Cheng, Peng; Chen, Shu; Wang, Ying; Zhou, Hu; Huang, Meijuan; Song, Yanping; Jin, Chenghao; Zhang, Donglei; Chen, Lingling; Liu, Wei; Zhang, Lei; Xue, Feng; Yang, Renchi"
作者地址："[Dou, Xueqing; Zhang, Wenhui; Zhang, Donglei; Chen, Lingling; Liu, Wei; Zhang, Lei; Xue, Feng; Yang, Renchi] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Expt Hematol, Natl Clin Res Ctr Blood Dis,Tianjin Key Lab Gene, Haihe Lab Cell Ecosyst,Inst Hematol,CAMS Key Lab, 288 Nanjing Rd, Tianjin 300020, Peoples R China; [Dou, Xueqing; Zhang, Wenhui; Zhang, Donglei; Chen, Lingling; Liu, Wei; Zhang, Lei; Xue, Feng; Yang, Renchi] Chinese Acad Med Sci & Peking Union Med Coll, Blood Dis Hosp, Tianjin Key Lab Gene Therapy Blood Dis, CAMS Key Lab Gene Therapy Blood Dis, 288 Nanjing Rd, Tianjin 300020, Peoples R China; [Dou, Xueqing] Soochow Univ, Natl Clin Res Ctr Hematol Dis, Jiangsu Inst Hematol, Affiliated Hosp 1, Suzhou, Peoples R China; [Poon, Man-Chiu] Univ Calgary, Dept Med, Cumming Sch Med, Calgary, AB, Canada; [Poon, Man-Chiu] Univ Calgary, Cumming Sch Med, Dept Pediat & Oncol, Calgary, AB, Canada; [Poon, Man-Chiu] Alberta Hlth Serv, Southern Alberta Rare Blood & Bleeding Disorders, Comprehens Care Program, Foothills Hosp, Calgary, AB, Canada; [Zhang, Xinsheng] Shandong Blood Ctr, Shandong Hemophilia Treatment Ctr, Jinan, Peoples R China; [Wu, Runhui] Capital Med Univ, Beijing Childrens Hosp, Beijing, Peoples R China; [Feng, Xiaoqin] Southern Med Univ, Nanfang Hosp, Guangzhou, Peoples R China; [Yang, Linhua] Shanxi Med Univ, Hosp 2, Taiyuan, Peoples R China; [Cheng, Peng] Guangxi Med Univ, Dept Hematol, Affiliated Hosp 1, Nanning, Peoples R China; [Chen, Shu] Chongqing Med Univ, Dept Hematol, Affiliated Hosp 2, Chongqing, Peoples R China; [Wang, Ying] Shenzhen Childrens Hosp, Shenzhen, Peoples R China; [Zhou, Hu] Zhengzhou Univ, Affiliated Canc Hosp, Henan Canc Hosp, Zhengzhou, Peoples R China; [Huang, Meijuan] Fujian Med Univ, Fujian Inst Haematol, Union Hosp, Fuzhou, Peoples R China; [Song, Yanping] Xian Cent Hosp, Xian, Peoples R China; [Jin, Chenghao] Jiangxi Prov Peoples Hosp, Dept Hematol, Nanchang, Jiangxi, Peoples R China"
通信作者："Xue, F; Yang, RC (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Expt Hematol, Natl Clin Res Ctr Blood Dis,Tianjin Key Lab Gene, Haihe Lab Cell Ecosyst,Inst Hematol,CAMS Key Lab, 288 Nanjing Rd, Tianjin 300020, Peoples R China.; Xue, F; Yang, RC (通讯作者)，Chinese Acad Med Sci & Peking Union Med Coll, Blood Dis Hosp, Tianjin Key Lab Gene Therapy Blood Dis, CAMS Key Lab Gene Therapy Blood Dis, 288 Nanjing Rd, Tianjin 300020, Peoples R China."
来源：HAEMOPHILIA
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:000859510700001
JCR分区：Q2
影响因子：3.9
年份：2022
卷号：
期号：
开始页：
结束页：
文献类型：Article; Early Access
关键词：anaphylaxis; China; haemophilia B; F9 gene mutation; immune tolerance induction; inhibitor
摘要："Introduction The development of inhibitors against factor FIX (FIX) is the most serious complication of FIX replacement therapy in haemophilia B (HB) patients. Currently, only few cohorts of HB inhibitor patients have been reported worldwide. Aim This Chinese nationwide study of HB inhibitor patients explored their risk factors for FIX inhibitor development and experience on their management. Methods We retrospectively analysed patient characteristics, F9 genotypes, treatment strategies and outcomes of HB inhibitor patients registered to the Chinese National Registry and Patient Organization Registry. Results Forty-four unique HB inhibitor patients were identified in 4485 unique HB patients registered by year 2021 to the two Registries. Inhibitor diagnosis were usually delayed and the low prevalence (.98%) may suggest some inhibitor patients were not identified. Their median age at inhibitor diagnosis was 7.5 (IQR, 3.0-14.8) years. Most patients (95.5%) had high-titre inhibitors. Allergic/Anaphylactic reactions occurred in 59.1% patients. Large deletions and nonsense mutations were the most common F9 mutation types in our FIX inhibitor patients. Patients with large F9 gene deletions were more likely to develop inhibitors (p = .0002), while those with missense mutations had a low risk (p < .0001). Thirteen (29.5%) patients received immune tolerance induction (ITI) therapy using low-dose prothrombin complex concentrate regimens. Twelve completed ITI with three (25.0%) achieving success. Nephrotic syndrome developed in two (16.7%) patients during ITI. Conclusion This study reports the largest Chinese cohort of HB inhibitor patients. Large deletions were most significantly associated with inhibitor development. Low-dose ITI might be feasible for FIX inhibitor eradication."
基金机构：Non-profit Central Research Institute Fund of CAMS [2020-PT310-011]; CAMS Innovation Fund for Medical Sciences [2021-I2M-1-003]
基金资助正文："the Non-profit Central Research Institute Fund of CAMS, Grant/Award Number: 2020-PT310-011; CAMS Innovation Fund for Medical Sciences, Grant/Award Number: 2021-I2M-1-003"
