Fox Lucy C, Cohney Solomon J, Kausman Joshua Y, Shortt Jake, Hughes Peter D, Wood Erica M, Isbel Nicole M, de Malmanche Theo, Durkan Anne, Hissaria Pravin, Blombery Piers, Barbour Thomas D
Transfusion Research Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Nephrology (Carlton). 2018 Jun;23(6):507-517. doi: 10.1111/nep.13234.
Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.
血栓性微血管病（TMA）可在多种临床情况下出现，有可能导致肾脏、大脑、胃肠道和心脏出现严重功能障碍。所有血小板减少和贫血患者均应考虑TMA，应立即要求血液学实验室在血涂片上查找红细胞碎片。虽然任何病因的TMA通常都需要及时治疗，但在血栓性血小板减少性紫癜（TTP）和非典型溶血性尿毒症综合征（aHUS）中尤其如此，这两种疾病中器官衰竭可能迅速、不可逆且致命。对于所有成年人，若可能诊断为TTP，应在就诊后4 - 8小时内紧急开始经验性血浆置换（PE），等待ADAMTS13活性（一种去整合素和金属蛋白酶，含血小板反应蛋白基元13）检测结果。在进行任何血浆治疗之前，应采集柠檬酸钠血浆样本进行ADAMTS13检测。在儿童中，由大肠杆菌感染引起的志贺毒素相关性溶血性尿毒症综合征（STEC - HUS）是TMA最常见的病因，采用支持性治疗。如果已排除TTP和STEC - HUS，则应考虑aHUS的诊断，其治疗方法是使用单克隆补体C5抑制剂依库珠单抗。虽然除了少数鉴定出抗H因子自身抗体的患者外，通常无法早期确诊aHUS，但基因检测最终在相当一部分aHUS病例中揭示了与补体相关的突变。存在其他与TMA相关的情况（如感染、妊娠/产后和恶性高血压）并不排除TTP或aHUS作为TMA的潜在病因。
