Pathophysiology and Treatment of Thrombotic Microangiopathy

血栓性微血管病的特征是微血管病性溶血性贫血、血小板减少和由微血管血栓形成引起的组织损伤。血栓性微血管病的临床表现差异很大，部分取决于诱发条件，如感染，癌症，器官移植，恶性高血压，妊娠毒血症和各种药物。血栓形成时 微血管病发生在成人中，没有继发原因，在大多数情况下，肾损伤是次要特征，神经系统症状突出;这种综合征称为特发性血栓性血小板减少性紫癜（特发性TTP），通常是由于ADAMTS 13的获得性自身免疫缺陷，ADAMTS 13是一种切割血管性血友病因子（VWF）并抑制血小板血栓生长的金属蛋白酶。在一些 在临床相似的病例中，ADAMTS 13水平正常，TTP的原因几乎总是未知的。 严重ADAMTS 13缺乏的患者通常对血浆置换有反应，该亚组的死亡率为v15%，尽管高滴度的抑制性自身抗体与疾病复发的高可能性相关。相比之下，可检测到ADAMTS 13活性的患者几乎从未复发，血浆置换是否能改善其生存率尚不确定。一些研究表明ADAMTS 13活性和抑制剂 分析提供了有用的预后信息，但目前的测试在速度和灵敏度方面有明显的缺点，特别是对于抑制剂检测。

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.