Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
Canadian Blood Services, Hamilton, ON, Canada.
Br J Haematol. 2017 Apr;177(2):198-207. doi: 10.1111/bjh.14603. Epub 2017 Apr 3.
Heparin-induced thrombocytopenia (HIT) is a serious drug reaction that leads to a decrease in platelet count and a high risk of thrombosis. HIT patients produce pathogenic immunoglobulin G (IgG) antibodies that bind to complexes of platelet factor-4 (PF4) and heparin. HIT immune complexes crosslink Fc-receptors resulting in platelet and monocyte activation. These events lead to the release of procoagulant chemokines and tissue factor, which together create an intensely prothrombotic state. HIT represents an atypical immune response because it has features of both T cell-dependent and T cell-independent mechanisms. The disorder is characterized by newly formed anti-PF4/heparin IgG antibodies, which are characteristic of a T cell-dependent mechanism; however, re-exposure to heparin, months after HIT, does not lead to a memory response, which is consistent with a T cell-independent mechanism. In this review, we discuss the immunobiological events that can explain these features, including the role for T cell-dependent and T cell-independent mechanisms in HIT antibody generation, the immunogenic characteristics of the PF4/heparin antigen, and the concept of a temporary loss in immune regulation contributing to the onset of HIT. We also present a novel immunobiological model to explain the atypical immune response that is characteristic of HIT.
肝素诱导的血小板减少症（HIT）是一种严重的药物反应，可导致血小板计数减少和血栓形成风险增加。HIT 患者会产生致病性免疫球蛋白 G（IgG）抗体，该抗体与血小板因子 4（PF4）和肝素的复合物结合。HIT 免疫复合物交联 Fc 受体，导致血小板和单核细胞活化。这些事件导致促凝趋化因子和组织因子的释放，共同导致强烈的促血栓形成状态。HIT 代表一种非典型的免疫反应，因为它具有 T 细胞依赖性和 T 细胞非依赖性机制的特征。该疾病的特征是新形成的抗 PF4/肝素 IgG 抗体，这是 T 细胞依赖性机制的特征；然而，HIT 发生数月后再次暴露于肝素不会导致记忆反应，这与 T 细胞非依赖性机制一致。在这篇综述中，我们讨论了可以解释这些特征的免疫生物学事件，包括 T 细胞依赖性和 T 细胞非依赖性机制在 HIT 抗体产生中的作用、PF4/肝素抗原的免疫原性特征以及免疫调节暂时丧失导致 HIT 发病的概念。我们还提出了一种新的免疫生物学模型来解释 HIT 特有的非典型免疫反应。
