Factor IX inhibitors in haemophilia B: A report of National Haemophilia Registry in China
Xueqing Dou
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
Xueqing Dou and Wenhui Zhang have equal contribution.
Search for more papers by this authorWenhui Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Xueqing Dou and Wenhui Zhang have equal contribution.
Search for more papers by this authorMan-Chiu Poon
Departments of Medicine, Pediatrics and Oncology, Cumming School of Medicine, University of Calgary, and the Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Foothills Hospital, Alberta Health Services, Calgary, Alberta, Canada
Search for more papers by this authorXinsheng Zhang
Shandong Hemophilia Treatment Center, Shandong Blood Center, Jinan, China
Search for more papers by this authorRunhui Wu
Beijing Children's Hospital, Capital Medical University, Beijing, China
Search for more papers by this authorXiaoqin Feng
Nanfang Hospital, Southern Medical University, Guangzhou, China
Search for more papers by this authorLinhua Yang
Second Hospital of Shanxi Medical University, Taiyuan, China
Search for more papers by this authorPeng Cheng
Department of Hematology, Guangxi Medical University First Affiliated Hospital, Nanning, China
Search for more papers by this authorShu Chen
Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorHu Zhou
The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer hospital, Zhengzhou, China
Search for more papers by this authorMeijuan Huang
Fujian Medical University Union Hospital, Fujian Institute of Haematology, Fuzhou, China
Search for more papers by this authorChenghao Jin
Department of Hematology, Jiangxi Provincial People's Hospital, Nanchang, China
Search for more papers by this authorDonglei Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Search for more papers by this authorLingling Chen
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Search for more papers by this authorWei Liu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Search for more papers by this authorLei Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Search for more papers by this authorCorresponding Author
Feng Xue
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Correspondence
Feng Xue, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, 288 Nanjing Road, Tianjin 300020, PR China.
Email: [email protected]
Renchi Yang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, 288 Nanjing Road, Tianjin 300020, PR China.
Email:[email protected]
Search for more papers by this authorCorresponding Author
Renchi Yang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Correspondence
Feng Xue, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, 288 Nanjing Road, Tianjin 300020, PR China.
Email: [email protected]
Renchi Yang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, 288 Nanjing Road, Tianjin 300020, PR China.
Email:[email protected]
Search for more papers by this authorXueqing Dou
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
Xueqing Dou and Wenhui Zhang have equal contribution.
Search for more papers by this authorWenhui Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Xueqing Dou and Wenhui Zhang have equal contribution.
Search for more papers by this authorMan-Chiu Poon
Departments of Medicine, Pediatrics and Oncology, Cumming School of Medicine, University of Calgary, and the Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Foothills Hospital, Alberta Health Services, Calgary, Alberta, Canada
Search for more papers by this authorXinsheng Zhang
Shandong Hemophilia Treatment Center, Shandong Blood Center, Jinan, China
Search for more papers by this authorRunhui Wu
Beijing Children's Hospital, Capital Medical University, Beijing, China
Search for more papers by this authorXiaoqin Feng
Nanfang Hospital, Southern Medical University, Guangzhou, China
Search for more papers by this authorLinhua Yang
Second Hospital of Shanxi Medical University, Taiyuan, China
Search for more papers by this authorPeng Cheng
Department of Hematology, Guangxi Medical University First Affiliated Hospital, Nanning, China
Search for more papers by this authorShu Chen
Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Search for more papers by this authorHu Zhou
The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer hospital, Zhengzhou, China
Search for more papers by this authorMeijuan Huang
Fujian Medical University Union Hospital, Fujian Institute of Haematology, Fuzhou, China
Search for more papers by this authorChenghao Jin
Department of Hematology, Jiangxi Provincial People's Hospital, Nanchang, China
Search for more papers by this authorDonglei Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Search for more papers by this authorLingling Chen
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Search for more papers by this authorWei Liu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Search for more papers by this authorLei Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Search for more papers by this authorCorresponding Author
Feng Xue
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Correspondence
Feng Xue, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, 288 Nanjing Road, Tianjin 300020, PR China.
Email: [email protected]
Renchi Yang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, 288 Nanjing Road, Tianjin 300020, PR China.
Email:[email protected]
Search for more papers by this authorCorresponding Author
Renchi Yang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
Correspondence
Feng Xue, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, 288 Nanjing Road, Tianjin 300020, PR China.
Email: [email protected]
Renchi Yang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, 288 Nanjing Road, Tianjin 300020, PR China.
Email:[email protected]
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST
Renchi Yang has received speaker/consultancy fees from Novo Nordisk, Pfizer, Roche, Sanofi and Takeda. Man-Chiu Poon has received speaker/consultancy fees from Bayer, Bioverativ/Sanofi, CSL-Behring, Novo Nordisk, Pfizer, Roche and Takeda and has received grant funding from Bayer and CSL-Behring. The remaining authors have no disclosures to report.
Open Research
DATA AVAILABILITY STATEMENT
All data included in this study are available upon request by contact with the corresponding author.
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