HZRM Hemophilia Center Rhine-Main, Frankfurt-Mörfelden, Mörfelden-Walldorf, Germany.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Haemophilia. 2022 May;28 Suppl 4:111-118. doi: 10.1111/hae.14553.
Factor (F) VIII inhibitors develop in around 30% of previously untreated patients (PUPs) with severe haemophilia, to a lesser extend in moderate and mild haemophilia A and in up to 10% in severe haemophilia B. Diagnostic challenges and questions remain including access to high quality testing, the role for functional inhibitor testing and binding antibody testing, and the adaptations needed in the presence of non-factor replacement therapy. Despite significant gains in knowledge there are still many unanswered questions underlying the immunologic mechanisms of inhibitor development and tolerance. Therapeutic options include eradication of inhibitors using immune tolerance induction therapy (ITI), prophylaxis with bypassing agents (i.e., recombinant activated factor VII /rFVIIa or activated prothrombin complex concentrate/aPCC) or non-factor replacement therapies (e.g., emicizumab) and treatment of bleeds or coverage of surgeries/invasive procedure. Recently a haemophilia centre capacity building program was launched in China to further develop the infrastructure and support needed to improve the diagnosis of haemophilia, detection of inhibitors, and continue to improve the care of patients with haemophilia and inhibitors.
VIII 因子抑制剂在约 30%的未经治疗的重度血友病患者(PUP)中产生,在中度和轻度血友病 A 中产生的程度较轻,在重度血友病 B 中高达 10%。诊断方面仍然存在挑战和问题,包括能否获得高质量的检测、功能性抑制剂检测和结合抗体检测的作用,以及在非因子替代疗法存在的情况下需要进行哪些调整。尽管在知识方面取得了重大进展,但在抑制剂产生和耐受的免疫机制方面仍有许多未解答的问题。治疗选择包括使用免疫耐受诱导疗法(ITI)消除抑制剂、使用旁路制剂(即重组活化因子 VII/rFVIIa 或活化的凝血酶原复合物浓缩物/aPCC)或非因子替代疗法(例如,emicizumab)进行预防,以及治疗出血或手术/有创性操作的覆盖。最近,中国启动了血友病中心能力建设计划,以进一步发展基础设施和支持,以改善血友病的诊断、抑制剂的检测,并继续改善血友病和抑制剂患者的护理。