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.
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.
Br J Haematol. 2021 Mar;192(5):900-908. doi: 10.1111/bjh.17322. Epub 2021 Feb 3.
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.
同种异体抗体（抑制剂）的产生是甲型血友病（HA）患者接受 FVIII 替代治疗后最严重的并发症。我们在中国开展了一项针对有抑制剂的 HA 患者的全国性研究，以评估该人群的状况和管理。该研究回顾性分析了中国各地登记的 493 例抑制剂患者（466 例严重 HA 和 27 例非严重 HA）的患者特征、临床病史、表现、治疗策略以及个体血友病护理。在严重 HA 患者中，抑制剂诊断时的中位（四分位间距）年龄为 13（5-28）岁，在非严重 HA 患者中为 24（10.5-39.5）岁。大多数患者（85%）有高滴度抑制剂。76.2%和 29.2%的患者分别使用了凝血酶原复合物浓缩物和重组活化凝血因子 VII 治疗急性出血。仅有 22.3%的患者接受了免疫耐受诱导（ITI）治疗，其中 64.9%的患者达到了抑制剂滴度阴性。在未接受 ITI 治疗的患者中，17.7%的患者抑制剂滴度转为阴性，且峰值抑制剂滴度较低的患者更有可能自发获得阴性滴度（比值比 11.524，95%置信区间 5.222-25.432；P=0.000）。我们记录到有 3.2%的患者因血友病相关危及生命的出血而死亡。
