Department of Pathology and Molecular Medicine, Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
J Thromb Haemost. 2011 Jul;9 Suppl 1:105-17. doi: 10.1111/j.1538-7836.2011.04322.x.
The current major problem with HIT is its overdiagnosis. This concept follows from the HIT central paradigm: HIT is caused by a subset of antibodies against platelet factor 4 (PF4)/heparin complexes that have strong platelet-activating properties. Prospective studies show that only a minority of sera containing such antibodies exhibit platelet-activating properties. Ironically, the earliest tests for HIT--platelet activation assays--remain today the most diagnostically useful, particularly the washed platelet assays. But the wider application of PF4-dependent immunoassays, and their much greater sensitivity for the larger subset of non-platelet-activating (and non-HIT-inducing) antibodies, has resulted in HIT overdiagnosis in many centres. Studies of anti-PF4/heparin immunization in diverse clinical situations have provided insights into the factors that influence the HIT immune response. Besides the conundrum of anticoagulant-induced thrombosis (including its potentiation of coumarin-induced microthrombosis), HIT evinces numerous other paradoxes: (i) it is a platelet-activating disorder with venous thrombosis as its predominant clinical manifestation; (ii) 'delayed-onset' (or 'autoimmune') HIT can lead to dramatic worsening of HIT-associated thrombosis despite cessation of heparin; (iii) partial thromboplastin time (PTT) monitoring of direct thrombin inhibitor treatment - and confounding of PTT monitoring by HIT-associated consumptive coagulopathy - infers that the worst subset of HIT patients may fail this therapeutic approach; (iv) the highly sulfated pentasaccharide anticoagulant, fondaparinux, can (rarely) cause HIT yet appears to be an effective treatment for this disorder; and (v) the transience of the HIT immune response means that many patients with previous HIT can safely receive future heparin.
目前 HIT 的主要问题是其过度诊断。这一概念源于 HIT 的中心范式：HIT 是由一组针对血小板因子 4（PF4）/肝素复合物的抗体引起的，这些抗体具有强烈的血小板激活特性。前瞻性研究表明，只有少数含有此类抗体的血清表现出血小板激活特性。具有讽刺意味的是，最早用于检测 HIT 的测试——血小板激活测定法——至今仍是最具诊断价值的方法，尤其是洗涤血小板测定法。但是，更广泛地应用 PF4 依赖性免疫测定法，以及它们对更大比例非血小板激活（和非 HIT 诱导）抗体的更高敏感性，导致许多中心出现 HIT 过度诊断。在不同临床情况下对抗 PF4/肝素免疫接种的研究提供了对影响 HIT 免疫反应的因素的深入了解。除了抗凝剂诱导的血栓形成的难题（包括其对香豆素诱导的微血栓形成的增强作用）之外，HIT 还表现出许多其他悖论：（i）它是一种血小板激活障碍，其主要临床表现为静脉血栓形成；（ii）“迟发性”（或“自身免疫性”）HIT 可导致肝素停用后 HIT 相关血栓形成急剧恶化；（iii）直接凝血酶抑制剂治疗的部分凝血活酶时间（PTT）监测——以及 HIT 相关消耗性凝血障碍对 PTT 监测的混淆——推断出最严重的 HIT 患者可能无法接受这种治疗方法；（iv）高度硫酸化的五糖抗凝剂，磺达肝素，可（罕见）引起 HIT，但似乎是治疗该疾病的有效方法；（v）HIT 免疫反应的短暂性意味着许多有过 HIT 的患者可以安全地接受未来的肝素。
