Nurden Paquita, Clofent-Sanchez Gisèle, Jais Catherine, Bermejo Emilse, Leroux Lionel, Coste Pierre, Nurden Alan T
IFR4/FR21, Laboratoire d'Hématologie, Hôpital Cardiologique, 33604 Pessac, France.
Thromb Haemost. 2004 Oct;92(4):820-8. doi: 10.1160/TH04-04-0237.
Abciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percutaneous coronary intervention. We now report on the immunologic origin of thrombocytopenia developing between 7 and 12 days after the onset of abciximab infusion. Antibodies directed against abciximabcoated platelets were located in 5 patients with delayed thrombocytopenia, just as they were present in a patient whose platelet count fell within a few hours after receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using control platelets in the monoclonal antibody immobilization of platelet antigens assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG antibodies specific for platelets sensitized with abciximab was confirmed by flow cytometry. They were not located in 13 patients receiving abciximab but whose platelet counts remained stable. For three patients, antibodies were transient and their presence related to the extent of the thrombocytopenia. Surprisingly, antibodycontaining plasma from three patients induced abciximabdependent activation and aggregation of normal platelets, a finding confirmed by electron microscopy. Immunogold labeling revealed that abciximab was associated with platelets in the aggregate, suggesting that its inhibitory effect was overcome by the platelet stimulation. In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic.
阿昔单抗是一种抗糖蛋白IIb-IIIa药物，广泛用于预防经皮冠状动脉介入治疗期间的血栓形成并发症。我们现在报告阿昔单抗输注开始后7至12天出现的血小板减少症的免疫起源。在5例迟发性血小板减少症患者中发现了针对阿昔单抗包被血小板的抗体，就像在一名接受该药物后数小时内血小板计数下降的患者中一样。在使用抗糖蛋白IIb单克隆抗体SZ22进行的血小板抗原单克隆抗体固定试验（MAIPA）中，用对照血小板在血清中检测到了阿昔单抗依赖性IgG抗体。通过流式细胞术证实了存在对用阿昔单抗致敏的血小板具有特异性的IgG抗体。在13例接受阿昔单抗但血小板计数保持稳定的患者中未发现此类抗体。对于3例患者，抗体是短暂的，其存在与血小板减少的程度有关。令人惊讶的是，3例患者含有抗体的血浆诱导了正常血小板的阿昔单抗依赖性激活和聚集，这一发现通过电子显微镜得到证实。免疫金标记显示阿昔单抗与聚集体中的血小板相关，表明其抑制作用被血小板刺激所克服。总之，这些结果表明阿昔单抗依赖性血小板减少症可能会延迟出现，并可能具有促血栓形成作用。
