Abstract：
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease in which blood cells lack anchored proteins that regulate the complement system. The erythrocytes are then destroyed because of uncontrolled complement activity, leading to intravascular hemolysis (IVH) and a high risk of thrombosis outcome. A huge alteration in the treatment of the disease was the development of terminal complement inhibitors, with the achievement of IVH blockade, reduction or abolishment of red blood cell (RBC) transfusions, and thromboembolic events prevention. However, patients treated with these inhibitors can still present extravascular hemolysis (EVH) caused by C3 activation and residual IVH or clinically relevant levels of breakthrough hemolysis (BTH). Proximal complement inhibitors turned out to be the key to the solution of this problem by targeting components of the proximal complement pathway, avoiding intra and extravascular hemolysis. FDA approved eculizumab, ravulizumab (terminal inhibitors), pegcetacoplan, iptacopan, and danicopan (proximal inhibitors) as a treatment for PNH so far. Various clinical trials are underway to find the most effective method to treat patients with PNH. This review aimed to summarize 71 registered clinical trials in the ClinicalTrials.gov database with the various treatment drugs, possible mechanisms, and novel findings related to PNH treatment.
摘要：
阵发性睡眠性血红蛋白尿（PNH）是一种罕见的，血细胞缺乏调节补体系统的锚定蛋白的获得性疾病。然后，由于不受控制的补体活性，红细胞被破坏，导致血管内溶血（IVH）和血栓形成结果的高风险。治疗该疾病的一个巨大改变是末端补体抑制剂的发展，随着IVH封锁的实现，减少或废除红细胞（RBC）输血，和血栓栓塞事件的预防。然而,接受这些抑制剂治疗的患者仍可出现由C3激活和残余IVH引起的血管外溶血(EVH)或临床相关水平的突破性溶血(BTH).通过靶向近端补体途径的成分，近端补体抑制剂被证明是解决这一问题的关键，避免血管内和血管外溶血。FDA批准依库珠单抗，ravulizumab（终末抑制剂），pegcetacoplan,iptacopan,和danicopan（近端抑制剂）作为PNH的治疗。正在进行各种临床试验，以寻找治疗PNH患者的最有效方法。这篇综述旨在总结ClinicalTrials.gov数据库中涉及各种治疗药物的71项注册临床试验，可能的机制，以及与PNH治疗相关的新发现。
