Heamatology Department, New South Wales Health Pathology, Kogarah and Sutherland Campuses, Sydney, NSW, Australia.
Heamatolgy Department, St George and Sutherland Hospitals, Sydney, NSW, Australia.
Int J Lab Hematol. 2020 Jun;42 Suppl 1:25-32. doi: 10.1111/ijlh.13223.
Heparin-induced thrombocytopenia (HIT) is an immune reaction to heparin. It often causes severe thrombosis which may lead to limb gangrene and thrombosis-associated death. The concept of its pathogenesis has been evolving during the past five decades. Initially, HIT was thought to be caused by disseminated intravascular coagulation. Later it became clear that HIT was mediated by an immune mechanism whereby an IgG antibody induced platelet aggregation, release of procoagulant materials and consequently thrombus formation. The antigen comprises Platelet Factor 4 (PF4) and heparin which have a tendency to form ultralarge complexes. The HIT immune response has atypical features. IgG antibody appears early without IgM precedence and lasts transiently. One explanation is that there is prior priming by bacterial infection. Another unique characteristic is that it is processed as if it is a particulate antigen involving complement activation and B cells. Antigen-presenting cells/monocytes are also involved but the role of T cells is controversial. Recent advances have provided new insights into the underlying mechanisms of HIT-related thrombosis. Previously, platelets were believed to play a central role; their activation and consequently the induction of blood coagulation was the basis of the hypercoagulability in HIT. More recently, several studies have provided clear evidence that neutrophil and NETosis, monocytes and endothelial cells contribute significantly to the thrombosis in HIT. These new insights may result in development of better diagnostic laboratory assays and more effective treatments for HIT.
肝素诱导的血小板减少症（HIT）是一种针对肝素的免疫反应。它常导致严重的血栓形成，可能导致肢体坏疽和与血栓相关的死亡。其发病机制的概念在过去五十年中一直在发展。最初，HIT 被认为是由弥漫性血管内凝血引起的。后来清楚的是，HIT 是由免疫机制介导的，其中 IgG 抗体诱导血小板聚集、释放促凝物质，进而导致血栓形成。抗原包括血小板因子 4（PF4）和肝素，它们有形成超大复合物的倾向。HIT 的免疫反应具有非典型特征。IgG 抗体在没有 IgM 前期的情况下早期出现，并持续短暂。一种解释是存在细菌感染的预先致敏。另一个独特的特征是，它被处理为似乎是一种涉及补体激活和 B 细胞的颗粒性抗原。抗原呈递细胞/单核细胞也参与其中，但 T 细胞的作用存在争议。最近的进展为 HIT 相关血栓形成的潜在机制提供了新的见解。以前，血小板被认为起着核心作用；它们的激活，进而血液凝固的诱导是 HIT 中高凝状态的基础。最近，几项研究提供了明确的证据，表明中性粒细胞和 NETosis、单核细胞和内皮细胞对 HIT 中的血栓形成有重要贡献。这些新的见解可能导致更好的诊断实验室检测方法和更有效的 HIT 治疗方法的发展。
