Yenerel Mustafa N
İstanbul University İstanbul Faculty of Medicine, Department of Internal Medicine, Division of Hematology, İstanbul, Turkey. E-ma-il:
Turk J Haematol. 2014 Sep 5;31(3):216-25. doi: 10.4274/tjh.2013.0374.
Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA). It has an unfavorable outcome with death rates as high as 25% during the acute phase and up to 50% of cases progressing to end-stage renal failure. Uncontrolled complement activation through the alternative pathway is thought to be the main underlying pathopysiology of aHUS and corresponds to all the deleterious findings of the disease. Thrombotic thrombocytopenic purpura (TTP) and Shiga toxin-associated HUS are the 2 other important TMA diseases. Although differentiating HUS from TTP is relatively easy in children with a preceding diarrheal illness or invasive S. pneumoniae, differentiating aHUS from TTP or other microangiopathic disorders can present a major diagnostic challenge in adults. ADAMTS13 analysis is currently the most informative diagnostic test for differentiating TTP, congenital TTP, and aHUS. Today empiric plasma therapy still is recommended by expert opinion to be used as early as possible in any patient with symptoms of aHUS. The overall treatment goal remains restoration of a physiological balance between activation and control of the alternative complement pathway. So it is a reasonable approach to block the terminal complement complex with eculizumab in order to prevent further organ injury and increase the likelihood organ recovery. Persistence of hemolysis or lack of improvement of renal function after 3-5 daily plasmaphereses have to be regarded as the major criteria for uncontrolled TMA even if platelet count has normalized and as an indication to switch the treatment to eculizumab. Eculizumab has changed the future perspectives of patients with aHUS and both the FDA and the EMA have approved it as life-long treatment. However, there are still some unresolved issues about the follow-up such as the optimal duration of eculizumab treatment and whether it can be stopped or how to stop the therapy.
非典型溶血尿毒综合征（aHUS）是血栓性微血管病（TMA）的一种罕见形式。其预后不良，急性期死亡率高达25%，高达50%的病例会进展至终末期肾衰竭。通过替代途径的补体激活失控被认为是aHUS的主要潜在病理生理学机制，且与该疾病的所有有害表现相符。血栓性血小板减少性紫癜（TTP）和志贺毒素相关性溶血尿毒综合征是另外两种重要的TMA疾病。虽然在有前驱腹泻病或侵袭性肺炎链球菌感染的儿童中，将溶血尿毒综合征与TTP区分相对容易，但在成人中，将aHUS与TTP或其他微血管病性疾病区分可能是一项重大的诊断挑战。ADAMTS13分析目前是区分TTP、先天性TTP和aHUS最具信息价值的诊断测试。如今，专家意见仍建议对任何有aHUS症状的患者尽早进行经验性血浆治疗。总体治疗目标仍然是恢复替代补体途径激活与控制之间的生理平衡。因此，用依库珠单抗阻断末端补体复合物以防止进一步的器官损伤并增加器官恢复的可能性是一种合理的方法。即使血小板计数已恢复正常，在每日进行3 - 5次血浆置换后仍持续存在溶血或肾功能无改善，必须被视为未控制的TMA的主要标准，也是将治疗改为依库珠单抗的指征。依库珠单抗改变了aHUS患者的未来前景，美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）均已批准其作为终身治疗药物。然而，关于随访仍存在一些未解决的问题，例如依库珠单抗治疗的最佳持续时间以及是否可以停药或如何停药。
