阵发性睡眠性血红蛋白尿症补体抑制治疗研究进展  

Advances in complement inhibition therapy for paroxysmal nocturnal hemoglobinuria

作　　者：史忆萌 张凤奎 Shi Yimeng;Zhang Fengkui(National Clinical Research Center for Blood Diseases,State Key Laboratory of Experimental Hematology,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China;Tianjin Institutes of Health Science,Tianjin 301600,China)

机构地区：[1]国家血液系统疾病临床医学研究中心,血液与健康全国重点实验室,细胞生态海河实验室,中国医学科学院血液病医院(中国医学科学院血液学研究所),天津300020 [2]天津医学健康研究院,天津301600

出　　处：《中华血液学杂志》2025年第1期90-96,共7页Chinese Journal of Hematology

基　　金：中国医学科学院临床与转化医学研究专项(2023-I2M-C&T-B-107);中央高水平医院临床科研业务费(2022-PUMCH-C-026)。

摘　　要：阵发性睡眠性血红蛋白尿症(PNH)为一获得性克隆性造血异常,以往大部分PNH患者主要接受支持性治疗,生活质量差,死亡率高。下游补体C5抑制剂的出现则极大地改变了PNH的自然病程,在改善临床症状的同时,明显降低严重并发症的发生,提高了患者的生存率。尽管C5抑制剂在控制血管内溶血(IVH)和提高血红蛋白(HGB)水平方面效果显著,但是上游补体成分C3介导的血管外溶血(EVH)使得近半数治疗患者仍需要输血。上游补体抑制剂在控制IVH的同时,减少了C3片段的沉积,从而解决EVH的问题,进一步改善了PNH患者的临床结局。但是,由于补体激活的级联反应以及上游补体抑制剂治疗后PNH红细胞的比例累积增加,可能会增加发生更为严重的突破性溶血事件的风险。此外,补体抑制剂可能会增加感染风险,这也是当前需要关注的问题。Paroxysmal nocturnal hemoglobinuria(PNH)is an acquired clonal hematologic disorder.Historically,most PNH patients mainly received supportive treatment,which led to poor quality of life and high mortality rates.The advent of downstream complement C5 inhibitors has dramatically changed the natural course of PNH.These inhibitors alleviate clinical symptoms,significantly reduce severe complications,and improve survival rates.Despite their ability to control intravascular hemolysis and enhance hemoglobin levels,approximately half of the treated patients still require blood transfusions due to extravascular hemolysis(EVH)mediated by upstream complement component C3.Upstream complement inhibitors not only control IVH but also reduce the deposition of C3 fragments,thereby solving the problem of EVH and further improving the clinical outcomes of PNH patients.However,due to the cascade of complement activation and the increased accumulation of PNH red blood cells after treatment with upstream complement inhibitors,there may be an increased risk of more severe breakthrough hemolysis events.Additionally,the potential risk of infections associated with complement inhibitors is another issue that needs to be addressed.

关 键 词：血管内溶血 补体抑制剂 阵发性睡眠性血红蛋白尿症 血管外溶血 感染风险 临床结局 PNH 自然病程 

分 类 号：R55[医药卫生—血液循环系统疾病]