PharmGKB summary: heparin-induced thrombocytopenia pathway, adverse drug reaction.
PharmGKB summary: heparin-induced thrombocytopenia pathway, adverse drug reaction.
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DOI：
10.1097/fpc.0000000000000465
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发表时间：
2022-04-01
影响因子：
2.6
通讯作者：
Klein TE
中科院分区：
文献类型：
--
作者：
Miller E;Norwood C;Giles JB;Huddart R;Karnes JH;Whirl-Carrillo M;Klein TE
普通肝素（UFH）和低分子量肝素（LMWH）是治疗性抗凝的主要药物，具有多种理想的药理学特性，并且有大量证据支持其使用[1]。UFH和LMWH有可能引起肝素诱导的血小板减少症（HIT），这是一种脱靶、免疫介导的药物不良反应（ADR）。在接受肝素抗凝剂治疗的患者中，HIT发生率高达2.4%，死亡率超过30%，并可能导致灾难性血栓栓塞并发症，包括危及生命和肢体的血栓形成[2-5]。考虑到这些药物的广泛使用和该反应的严重程度，无法预测HIT构成了肝素抗凝治疗的相当大的责任。遗传变异有可能构成临床上可实施的生物标志物，预测HIT等ADR，提高肝素抗凝剂的安全性[6，7]。以前的研究旨在确定HIT的遗传影响主要是候选基因的研究，集中在FCGR 2A和HLA位点的多态性。全基因组关联研究（GWAS）也得到了相互矛盾的结果。在这里，我们回顾了HIT的病理生理学，影响HIT风险的可能生物学途径，以及与HIT遗传相关的证据。由于UFH和LMWH都有可能导致HIT，因此本总结将重点关注UFH，因为其HIT风险较高[1]。
Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are mainstays of therapeutic anticoagulation with multiple desirable pharmacologic traits and a wealth of evidence supporting their use [1]. UFH and LMWH have the potential to cause heparin-induced thrombocytopenia (HIT), an off-target, immune-mediated adverse drug reaction (ADR). HIT occurs in up to 2.4% of patients treated with heparin anticoagulants, has a greater than 30% mortality rate, and may result in catastrophic thromboembolic complications, including life-and limb-threatening thrombosis [2–5]. Considering the widespread use of these agents and the severity of this reaction, the inability to predict HIT constitutes a considerable liability for heparin anticoagulant treatment. Genetic variation has the potential to constitute clinically implementable biomarkers that predict ADRs such as HIT, improving the safety of heparin anticoagulants [6, 7]. Previous studies aimed at identifying genetic influences on HIT are primarily candidate gene studies that have focused on polymorphisms in FCGR2A and the HLA locus. Genomewide association studies (GWAS) have also been conducted with conflicting results. Here, we review the pathophysiology of HIT, the likely biological pathways influencing HIT risk, and the evidence of genetic associations with HIT. As both UFH and LMWH have the potential to cause HIT, this summary will focus on UFH due to its higher HIT risk [1].