血栓性微血管病(TMA)包括一系列以小血管凝血为特征的疾病,导致器官损伤。它可以表现为各种综合症,包括血栓性血小板减少性紫癜(TTP),溶血性尿毒综合征(HUS),和其他人,每种都有不同的病因和病理生理学。血栓-炎症在TMA发病机制中起重要作用:炎症介质诱导内皮损伤和血小板活化和凝血级联反应,导致微血管血栓形成。主要TMA,比如TTP,主要是由ADAMTS13金属蛋白酶活性不足引起的,由于抗体介导的抑制或内在的酶合成缺陷。在癌症患者中,观察到ADAMTS13水平显著降低,VWF水平相应升高.化疗进一步降低ADAMTS13水平和增加VWF水平,导致VWF/ADAMTS13比值升高和血栓形成风险增加。药物诱导的TMA(DITMA)可以由免疫介导的或非免疫介导的机制产生。COVID-19的严重病例可能导致综合征的收敛,包括弥散性血管内凝血(DIC),全身炎症反应综合征(SIRS),还有TMA.TMA的治疗包括确定根本原因,实施抑制补体激活的疗法,并提供支持性护理来管理并发症。血浆置换在TTP等条件下可能是有益的。及时诊断和治疗对于预防严重并发症和改善预后至关重要。
Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient
ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in
ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased
ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/
ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes.