Patients with haemophilia A with inhibitors in China: a national real-world analysis and follow-up
Xueqing Dou
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Search for more papers by this authorWei Liu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Search for more papers by this authorMan-Chiu Poon
Departments of Medicine, Pediatrics and Oncology, University of Calgary, Cumming School of Medicine and Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Foothills Medical Centre, Alberta Health Services, Calgary, AB, Canada
Search for more papers by this authorJingsheng Wu
First Affiliated Hospital, Chinese University of Science and Technology, Hefei, China
Search for more papers by this authorXiaojing Zeng
The Affiliated Hospital of Guizhou Medical University, Guiyang, China
Search for more papers by this authorRunhui Wu
Beijing Children's Hospital, Capital Medical University, Beijing, China
Search for more papers by this authorQun Hu
Department of Pediatric Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China
Search for more papers by this authorChengping Li
First Affiliated Hospital of Kunming Medical University, Kunming, China
Search for more papers by this authorXiaomin Wang
Xinjiang Uygur Autonomous Region People's Hospital, Urumchi, China
Search for more papers by this authorXuewen Song
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Search for more papers by this authorLingling Chen
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Search for more papers by this authorLei Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, 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, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Correspondence: Professor Feng Xue and Renchi Yang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, 288 Nanjing Road, Tianjin 300020, PR China.
E-mails: [email protected] and [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, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Correspondence: Professor Feng Xue and Renchi Yang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, 288 Nanjing Road, Tianjin 300020, PR China.
E-mails: [email protected] and [email protected]
Search for more papers by this authorXueqing Dou
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Search for more papers by this authorWei Liu
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Search for more papers by this authorMan-Chiu Poon
Departments of Medicine, Pediatrics and Oncology, University of Calgary, Cumming School of Medicine and Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Foothills Medical Centre, Alberta Health Services, Calgary, AB, Canada
Search for more papers by this authorJingsheng Wu
First Affiliated Hospital, Chinese University of Science and Technology, Hefei, China
Search for more papers by this authorXiaojing Zeng
The Affiliated Hospital of Guizhou Medical University, Guiyang, China
Search for more papers by this authorRunhui Wu
Beijing Children's Hospital, Capital Medical University, Beijing, China
Search for more papers by this authorQun Hu
Department of Pediatric Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China
Search for more papers by this authorChengping Li
First Affiliated Hospital of Kunming Medical University, Kunming, China
Search for more papers by this authorXiaomin Wang
Xinjiang Uygur Autonomous Region People's Hospital, Urumchi, China
Search for more papers by this authorXuewen Song
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Search for more papers by this authorLingling Chen
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Search for more papers by this authorLei Zhang
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, 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, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Correspondence: Professor Feng Xue and Renchi Yang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, 288 Nanjing Road, Tianjin 300020, PR China.
E-mails: [email protected] and [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, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China
Correspondence: Professor Feng Xue and Renchi Yang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, 288 Nanjing Road, Tianjin 300020, PR China.
E-mails: [email protected] and [email protected]
Search for more papers by this authorSummary
The development of alloantibodies (inhibitors) against coagulation factor VIII (FVIII) is the most serious complication of FVIII replacement therapy in patients with haemophilia A (HA). We carried out a nationwide study focussing on patients with HA with inhibitors in China to evaluate the condition and management of this population. The study retrospectively analysed patient characteristics, clinical history, manifestation, treatment strategy as well as individual haemophilia care of 493 patients with inhibitors (466 with severe HA and 27 with non-severe HA) registered all over China. The median (interquartile range) age at diagnosis of FVIII inhibitors was 13 (5–28) years in patients with severe HA and 24 (10·5–39·5) years in patients with non-severe HA. Most patients (85%) had high-titre inhibitors. Prothrombin complex concentrate and recombinant activated coagulation factor VII were used respectively in 76·2% and 29·2% of patients for acute bleeding. Only 22·3% of patients underwent immune tolerance induction (ITI) treatment, of whom 64·9% achieved negative inhibitor titre. In patients who did not undergo ITI, the inhibitors turned negative in 17·7%, and patients with low peak inhibitor titre were more likely to acquire negative titre spontaneously (odds ratio 11·524, 95% confidence interval 5·222–25·432; P = 0·000). We recorded that 3·2% of the patients died from haemophilia-related life-threatening bleeding.
Conflicts of interest
Renchi Yang has received speaker/consultancy fees from Bayer, Novo Nordisk, Pfizer, Roche 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 . Other authors declared no competing interests.
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