Serological features of antibodies to protamine inducing thrombocytopenia and thrombosis
Serological features of antibodies to protamine inducing thrombocytopenia and thrombosis
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鱼精蛋白抗体诱导血小板减少症和血栓形成的血清学特征
DOI：
10.1515/cclm-2014-0664
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
J. Amiral
中科院分区：
文献类型：
--
作者：
S. Panzer;A. Schiferer;B. Steinlechner;L. Drouet;J. Amiral
摘要背景：接受心肺转流术的患者中有相当一部分会产生抗鱼精蛋白抗体，伴或不伴血栓栓塞事件。研究方法：我们广泛研究了鱼精蛋白抗体的血清学特征，这些抗体是在六名临床疑似患有肝素诱导的血小板减少症（HIT）的患者中产生的。3例患者发生血栓形成事件。通过四种不同的市售免疫测定法、肝素-血小板聚集试验以及它们与肝素、血小板因子4（PF 4）、复合肝素-PF 4、鱼精蛋白和鱼精蛋白与肝素的复合物的结合特性来测试血清。还测试了来自四名患者的血清诱导血小板活化和血小板-单核细胞异型聚集体形成的能力。结果如下：ELISA试验Zymutest HIA在所有病例中均为强阳性，HPIA Asserachrome为临界值，凝胶离心试验PaDGIA在2例受试患者中为阳性。血小板聚集试验阴性。使用Zymutest HIA的变体，我们证明IgG抗体仅与鱼精蛋白或鱼精蛋白与肝素的复合物结合，但不与肝素或PF 4结合。血清诱导的血小板P-选择素表达和血小板-单核细胞聚集体的形成。1例患者的血液样本证实伴随血栓栓塞事件呈阳性。然而，与血栓栓塞事件相关的抗体和与血栓栓塞事件无关的抗体之间的血清学特征没有差异。结论：这些数据表明，鱼精蛋白诱导的抗体是特异性的，并可能诱导血小板活化，这解释了它们与血栓栓塞事件的关联。
Abstract Background: A significant proportion of patients undergoing cardiopulmonary bypass develop anti-protamine antibodies, with or without the association of thromboembolic events. Methods: We extensively investigated the serological features of protamine antibodies, which developed in six patients who were clinically suspected to have heparin-induced thrombocytopenia (HIT). Three patients had thrombotic events. Sera were tested by four different commercially available immunoassays, a heparin-platelet aggregation test, and for their binding properties to heparin, platelet factor 4 (PF4), complex heparin-PF4, protamine, and protamine complex with heparin. Sera from four patients were also tested for the capability to induce platelet activation and the formation of platelet-monocyte heterotypic aggregates. Results: The ELISA assay Zymutest HIA was strongly positive in all cases, the HPIA Asserachrome was borderline, and the gel centrifugation test PaDGIA was positive in two tested patients. Platelet aggregation tests were negative. Using a variation of the Zymutest HIA we demonstrate that IgG antibodies bound only to protamine or protamine complex with heparin, but not to heparin or PF4 only. Sera-induced platelet P-selectin expression and the formation of platelet-monocyte aggregates. Blood samples from one patient proofed positive concomitantly with the thromboembolic event. However, serological characteristics did not differ between antibodies associated with thromboembolic events from those without. Conclusions: These data show that protamine-induced antibodies are specific and may induce platelet activation, which explains their association with thromboembolic events.
肝素诱导的血小板减少症的机制基础。
影响因子：
2.5
作者：
Poncz,Mortimer
通讯作者：
Poncz,Mortimer