Institute for Immunology and Transfusion Medicine, University Medicine Ernst Moritz Arndt University Greifswald, Sauerbruchstrasse, 17487 Greifswald, Germany.
Expert Opin Pharmacother. 2012 May;13(7):987-1006. doi: 10.1517/14656566.2012.678834. Epub 2012 Apr 5.
Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic adverse effect of heparin treatment. The underlying cause is the formation of highly immunogenic complexes between negatively charged heparin and positively charged platelet factor 4 (PF4). Resulting antibodies against these PF4/heparin complexes can activate platelets via the platelet FcγIIa receptor, leading to thrombin generation and thus to the paradox of a prothrombotic state despite thrombocytopenia and application of heparin. Prompt diagnosis of HIT is important in order to change treatment to prevent severe thromboembolic complications. However, this is often difficult as thrombocytopenia is frequent in hospitalized patients and the commercially available laboratory tests for HIT antibodies have a high negative predictive value but only a poor positive predictive value. This leads to overdiagnosis and overtreatment of HIT, which also bear the risk for adverse outcomes.
This review aims at resuming recent data on HIT, thereby focusing on the role of new anticoagulants and providing a framework for diagnosis and treatment. Furthermore, it provides some insights into the pathogenesis of this peculiar adverse drug reaction and ventures a guess at its future relevance in clinical practice.
New drugs which are strongly negatively charged should be assessed for their capacity to form complexes with PF4. If they do so, they bear the risk of inducing a HIT-like immune response. The immunology of HIT is still largely unresolved. Understanding HIT might provide insights into other immune and autoimmune response mechanisms.
肝素诱导的血小板减少症（HIT）是肝素治疗中一种罕见但严重的促血栓形成的不良反应。其根本原因是带负电荷的肝素与带正电荷的血小板因子 4（PF4）之间形成了高度免疫原性的复合物。由此产生的针对这些 PF4/肝素复合物的抗体可以通过血小板 FcγIIa 受体激活血小板，导致凝血酶生成，从而导致尽管存在血小板减少症和肝素应用，但仍处于促血栓形成状态的悖论。及时诊断 HIT 非常重要，以便改变治疗方法以预防严重的血栓栓塞并发症。然而，这通常很困难，因为住院患者中血小板减少症很常见，并且商业上可用的 HIT 抗体实验室检测具有高阴性预测值，但阳性预测值却很差。这导致 HIT 的过度诊断和过度治疗，这也存在不良后果的风险。
本综述旨在总结关于 HIT 的最新数据，从而重点关注新型抗凝剂的作用，并为诊断和治疗提供框架。此外，它还深入探讨了这种特殊药物不良反应的发病机制，并对其在临床实践中的未来相关性进行了猜测。
应评估带强烈负电荷的新药与 PF4 形成复合物的能力。如果它们这样做，它们就有可能引起类似于 HIT 的免疫反应。HIT 的免疫学仍在很大程度上尚未解决。了解 HIT 可能会深入了解其他免疫和自身免疫反应机制。
