Department of Obstetrics, Gynecology and Perinatal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya Str. 8-2, 119991 Moscow, Russia.
Faculty of General Medicine, Russian University of Medicine, 4th Dolgorukovskaya Str., 127006 Moscow, Russia.
Int J Mol Sci. 2024 Aug 21;25(16):9055. doi: 10.3390/ijms25169055.
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.
血栓性微血管病（TMA）涵盖了一系列以小血管内血栓形成导致器官损伤为特征的疾病。它可以表现为各种综合征，包括血栓性血小板减少性紫癜（TTP）、溶血尿毒综合征（HUS）和其他综合征，每种综合征都有不同的病因和病理生理学。血栓炎症在 TMA 的发病机制中起着重要作用：炎症介质诱导内皮细胞损伤和血小板及凝血级联的激活，导致微血管血栓形成。原发性 TMA，如 TTP，主要是由于 ADAMTS13 金属蛋白酶活性缺乏引起的，要么是由于抗体介导的抑制，要么是由于内在酶合成缺陷。在癌症患者中，ADAMTS13 水平显著降低，VWF 水平相应升高。化疗进一步降低了 ADAMTS13 水平，增加了 VWF 水平，导致 VWF/ADAMTS13 比值升高和血栓形成风险增加。药物引起的 TMA（DITMA）可能由免疫介导或非免疫介导的机制引起。严重的 COVID-19 病例可能导致多种综合征的融合，包括弥散性血管内凝血（DIC）、全身性炎症反应综合征（SIRS）和 TMA。TMA 的治疗包括确定潜在原因，实施抑制补体激活的治疗，并提供支持性护理以处理并发症。在 TTP 等情况下，血浆置换可能有益。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。
