Pathophysiology and Treatment of Thrombotic Microangiopathy

血栓性微血管病以微血管病理性溶血性贫血、血小板减少和微血管血栓形成引起的组织损伤为特征。血栓性微血管病的临床表现差异很大，部分取决于感染、癌症、器官移植、恶性高血压、妊娠毒血症和各种药物等易感条件。当血栓形成时 微血管病变发生在没有继发性原因的成人中，在大多数情况下，肾脏损害是轻微的特征，神经症状突出；这种综合征被称为特发性血栓性血小板减少性紫癜(ITP)，通常是由于获得性自身免疫缺陷ADAMTS13，一种金属蛋白酶，裂解von Willetjrand因子(VWF)，抑制血小板血栓的生长。在一些 在临床相似的病例中，ADAMTS13水平正常，TTP的原因几乎总是未知的。 ADAMTS13严重缺乏的患者通常对血浆置换有反应，这一亚群的死亡率为v15%，尽管高滴度的抑制性自身抗体与疾病复发的可能性高相关。相比之下，ADAMTS13活性可检测到的患者几乎永远不会复发，血浆置换是否提高了他们的存活率尚不确定。多项研究表明，ADAMTS13的活性和抑制剂 检测提供了有用的预测信息，但目前的检测在速度和灵敏度方面存在重大缺陷，特别是在抑制物检测方面。

Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and tissue damage caused by microvascular thrombosis. Clinical manifestations of thrombotic microangiopathy vary considerably, depending in part on predisposing conditions such as infections, cancer, organ transplantation, malignant hypertension, toxemia of pregnancy, and a variety of drugs. When thrombotic microangiopathy occurs in adults without a secondary cause, in most cases renal damage is a minor feature and neurological symptoms are prominent; this syndrome is called idiopathic thrombotic thrombocytopenic purpura (idiopathic TTP) and usually is due to acquired, autoimmune deficiency of ADAMTS13, a metalloprotease that cleaves von Willetjrand factor (VWF) and inhibits the growth of platelet thrombi. In some clinically similar cases, ADAMTS13 levels are normal and the cause of TTP almost always is unknown. Patients with severe ADAMTS13 deficiency usually respond to plasma exchange and the mortality for this subgroup is v15%, although a high titer of inhibitory autoantibody correlates with high likelihood of relapsing disease. In contrast, patients with detectable ADAMTS13 activity almost never relapse, and whether plasma exchange improves their survival is uncertain. Several studies suggest that ADAMTS13 activity and inhibitor assays provide useful prognostic information, but current tests have significant shortcomings in terms of speed and sensitivity, especially for inhibitor detection.