Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins.
Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins.
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DOI：
10.1111/bjh.12521
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发表时间：
2013-10
影响因子：
6.5
通讯作者：
Aster R
中科院分区：
文献类型：
--
作者：
Sahud MA;Caulfield M;Clarke N;Koch R;Bougie D;Aster R
胺碘酮被认为是血小板减少症的一个原因，但其机制尚不清楚。我们在三名患者中进行了研究，以描述这种并发症的发病机制。使用常规血清学技术未发现胺碘酮依赖性血小板反应性抗体。然而，溶于甲醇并在水性缓冲液中稀释至1.0 mg/ml的水不溶性胺碘酮可重现地促进患者血清中IgG抗体与血小板的结合。固相分析鉴定了每例患者中血小板糖蛋白（GP）Ia/IIa（整联蛋白α2β1）特异性的药物依赖性抗体和1例患者中GPIIb/IIIa（αIIbβ3整联蛋白）特异性的第二抗体。当通过离子迁移率分析和透射电子显微镜研究时，发现血清学活性胺碘酮制剂（一种乳状混悬液）由直径2-30 nm的颗粒组成，典型的凝聚层，这是胺碘酮在水性介质中的特征状态。这些发现提供了证据，表明研究的3例患者中的血小板减少症是由血小板糖蛋白GPIa/IIa和/或GPIIb/IIIa特异性的药物依赖性抗体引起的。我们假设，在体内，胺碘酮可能会被纳入血小板糖蛋白中的隐匿性亲脂性结构域，在某些个体中产生免疫原性的结构修饰，并且产生的抗体可能会导致服用该药的人血小板破坏。
Amiodarone has been implicated as a cause of thrombocytopenia but the responsible mechanism is unknown. We performed studies in three patients to characterize the pathogenesis of this complication. No amiodarone-dependent, platelet-reactive antibodies were identified using conventional serological techniques. However, water-insoluble amiodarone solubilized in methanol and diluted to 1·0 mg/ml in aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum to platelets. Solid phase assays identified drug-dependent antibodies specific for platelet gly coproteins (GP)Ia/IIa (integrin α2β1) in each patient and a second antibody specific for GPIIb/IIIa (αIIbβ3 integrin) in one patient. When studied by ion mobility analysis and transmission electron microscopy, the serologically active amiodarone preparation, a milky suspension, was found to consist of particles 2–30 nm in diameter, typical of a coacervate, a state characteristic of amiodarone in aqueous medium. The findings provide evidence that thrombocytopenia in the three patients studied was caused by drug-dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into occult lipophilic domains in platelet glycoproteins, producing structural modifications that are immunogenic in some individuals, and that the resulting antibodies can cause platelet destruction in a person taking this drug.
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DOI：
10.1111/j.1538-7836.2009.03360.x
发表时间：
2009-06
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Aster RH;Curtis BR;McFarland JG;Bougie DW
通讯作者：
Bougie DW
影响因子：
2.3
作者：
Liu, XJ;Sahud, MA
通讯作者：
Sahud, MA
DOI：
10.1016/j.colsurfa.2005.11.014
发表时间：
2006-04-05
影响因子：
5.2
作者：
Sierra, MB;Messina, PV;Sarmiento, F
通讯作者：
Sarmiento, F
影响因子：
--
作者：
WEINBERGER, I;ROTENBERG, Z;AGMON, J
通讯作者：
AGMON, J
影响因子：
2.7
作者：
BETTAIEB, A;FROMONT, P;BIERLING, P
通讯作者：
BIERLING, P