Glycoprotein IIb/IIIa complex is the target in mirtazapine-induced immune thrombocytopenia
Glycoprotein IIb/IIIa complex is the target in mirtazapine-induced immune thrombocytopenia
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DOI：
10.1016/s1079-9796(03)00037-8
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发表时间：
2003-05-01
影响因子：
2.3
通讯作者：
Sahud, MA
中科院分区：
文献类型：
--
作者：
Liu, XJ;Sahud, MA
米氮平（MW 265.36）是哌嗪-氮平类的四环抗抑郁药，可增强中枢去甲肾上腺素能和血清素能活性，目前用作口服抗抑郁药。我们报告一例66岁患者在服用米氮平后发生的严重血小板减少症，提示免疫机制。本报告记录了第一例米氮平诱导的免疫性血小板减少症。采用铬（51）（Cr-51）溶血小板技术对患者血清进行药物性抗血小板抗体筛选。采用流式细胞术、单克隆抗体固定血小板抗原法（MAIPA）和免疫沉淀法对药物依赖性抗体进行表征。通过Cr-51血小板裂解技术，我们对米氮平诱导抗体的检测结果模棱两可。然而，患者的血清经流式细胞术检测为米氮平诱导抗体阳性。结果表明，在患者血清和终浓度为1.0 mmol/L的米氮平存在下，结合比为5.7（平均荧光强度）为强阳性。用5种不同的针对糖蛋白（GP）复合物Ib/IX、GPIIb/IIIa或gpiia /IIa的单克隆抗体，通过MAIPA检测发现该抗体与糖蛋白（GP） IIb/IIIa复合物结合。免疫沉淀研究表明，GPIIb/IIIa复合物在米氮平存在的情况下被抗体沉淀，而在米氮平不存在的情况下则没有。这些发现提供了对抗抑郁药米氮平敏感可引起免疫性血小板减少的证据。这是第一个充分记录的米氮平诱导的免疫性血小板减少症病例。(C) 2003 Elsevier Science（美国）版权所有。
Mirtazapine (MW 265.36), a tetracyclic antidepressant of the piperazine-azapine group which augments central noradrenergic and serotonergic activity, is currently used as an oral antidepressant. We report a case of severe thrombocytopenia in a 66-year-old patient occurring after mirtazapine administration, suggesting an immune mechanism. This report documents the first case of mirtazapine-induced immune thrombocytopenia. The patient's serum was screened for drug-induced anti-platelet antibody with the chromium(51) (Cr-51) platelet lysis technique. The drug-dependent antibody was characterized using flow cytometry, the monoclonal antibody immobilization of platelet antigens assay (MAIPA assay), and immunoprecipitation. By the Cr-51 platelet lysis technique, we obtained an equivocal result for the detection of mirtazapine-induced antibody. However, the patient's serum tested positive for mirtazapine-induced antibody by flow cytometry. The results showed that the binding ratio of 5.7 (mean fluorescence intensity) in the presence of the patient's serum and mirtazapine in a final concentration of 1.0 mmol/L was strongly positive. The antibody was found to bind the glycoprotein (GP) IIb/IIIa complex by MAIPA assay by using five different monoclonal antibodies against GP complexes Ib/IX, GPIIb/IIIa, or GPIa/IIa. Immunoprecipitation studies showed that the GPIIb/IIIa complex was precipitated by antibody in the presence, but not in the absence, of mirtazapine. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to the antidepressant mirtazapine. This is the first well-documented case of mirtazapine-induced immune thrombocytopenia. (C) 2003 Elsevier Science (USA). All rights reserved.