Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France.
Thromb Haemost. 2010 Mar;103(3):651-61. doi: 10.1160/TH09-08-0603. Epub 2010 Jan 13.
Our study concerns thrombocytopenia in patients with acute ischaemic coronary artery disease receiving anti-platelet drugs to the aIIbb3 integrin (GPIIb/IIIa). We have screened for drug-dependent antibodies (DDAB) in 18 patients who suffered a fall of > 50% in platelet count (9 patients had a nadir of <50,000 platelets/microl) after receiving abciximab and related results to clinical outcome. Serum or plasma was screened for DDAB using (i) a direct ELISA against purified aIIbb3, aIIbb3-abciximab complexes or abciximab alone, (ii) control platelets and flow cytometry and (iii) monoclonal antibody immobilisation of platelet antigens. DDAB were found for 11 patients, with aIIbb3 ELISA the most sensitive test. Progressive platelet consumption linked with haemoglobin loss and/or use of intra-aortic balloon pumping, another potential cause of a fall in platelet count, was also evaluated. DDAB were identified that recognised aIIbb3 associated with abciximab and/or abciximab alone. Screening of both progressive and delayed thrombocytopenia (appearing after 5 to 11 days) suggested that antibodies against abciximab preceded those recognising neo-epitopes on aIIbb3, with a time-dependent broadening of antibody specificities. Higher titres were seen after second abciximab use. Five antibodies were platelet-activating. In conclusion, the mechanisms responsible for this complication of anti-aIIbb3 therapy are multiple and often associated with a complex immune response.
我们的研究涉及接受抗血小板药物治疗 aIIbb3 整联蛋白（GPIIb/IIIa）的急性缺血性冠状动脉疾病患者的血小板减少症。我们在 18 名接受阿昔单抗治疗后血小板计数下降> 50%的患者（9 名患者血小板计数<50,000/μl）中筛选了药物依赖性抗体（DDAB），并将相关结果与临床结果相关联。使用（i）针对纯化的 aIIbb3、aIIbb3-阿昔单抗复合物或阿昔单抗单独的直接 ELISA、（ii）对照血小板和流式细胞术和（iii）血小板抗原的单克隆抗体固定化，筛选血清或血浆中的 DDAB。在 11 名患者中发现了 DDAB，其中 aIIbb3 ELISA 是最敏感的测试。还评估了与血红蛋白丢失和/或使用主动脉内球囊泵相关的进行性血小板消耗，这也是血小板计数下降的另一个潜在原因。鉴定出的 DDAB 可识别与阿昔单抗相关的 aIIbb3 和/或阿昔单抗本身。对进行性和延迟性血小板减少症（在 5 至 11 天后出现）的筛选表明，针对阿昔单抗的抗体先于针对 aIIbb3 上新表位的抗体，抗体特异性随时间而扩大。在第二次使用阿昔单抗后观察到更高的滴度。五种抗体具有血小板激活作用。总之，抗 aIIbb3 治疗这种并发症的机制是多方面的，并且常常与复杂的免疫反应有关。
