Progress in Research on Prevention and Treatment o...
Liu Shanxi1,Zhao Xiaoai2,Cheng Yimeng1
1.Shaanxi Yida Hemophilia Institute Xi'an 710032
2.First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061(https://www.daowen.com)
Abstract Hemophilia FⅧ/FⅨ inhibitor is a kind of specific neutralizing antibody,making treatment invalid, and increasing bleeding and the incidence of death and disability.It is a serious complication of hemophilia and also anew challenge.Risk factors associated with the production of inhibitors are related to genetic factors and environment, providing a direction for prevention.The present effective treatments of hemophilia inhibitor include bypass drugfor homeostasis and immune tolerance induction therapy to clear inhibitor and new homeostatic prophylaxis, but these still can't meet the needs.Recently, a variety of new hemostatic drugshave been developed, which have a long half-life and can be injected subcutaneously once every 4 weeks for prevention and treatment, with an annual bleeding rate of 0 and no inhibitor produced, making breakthroughs。
Key words Hemophilia; Inhibitor; Immune tolerance; Bypass for homeostasis; New homeostatic agent
血友病是一组出血、死亡及致残率极高的遗传性出血性疾病。半个世纪以来,凝血因子替代治疗使出血得到了有效控制[1-2],但伴随而来的是凝血因子Ⅷ/Ⅸ(FⅧ/FⅨ)抑制物的产生,灭活FⅧ/FⅨ活性,加重出血、死亡和致残率,成为血友病的严重并发症和新的挑战[3-4]。研究显示抑制物产生与遗传和环境等因素有关[3-4],但机理仍不明确。目前治疗血友病A并发抑制物的有效方法为旁路药物止血和免疫耐受诱导疗法清除抗体[3],但二者存在血栓形成和有效率(70%)低下缺陷[3]。最近研发的新型止血药(emicizumab)的特点是每4周皮下注射1次,进行有/无抑制物HA的预防和按需治疗,年化出血率(ABR)为0%,不产生抑制物,被誉为创新性、突破性进展[1-3],但经Ⅲ期临床试验,仍存在管理缺陷 [3]。现对血友病抑制物防治研究的进展及其合理应用予以综述。