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采用一种新型基于 ELISA 的血管扩张剂刺激磷酸化蛋白(VASP)磷酸化检测方法,鉴定 ACS 患者对 P2Y12 抑制剂的无应答。

Identification of poor response to P2Y12 inhibitors in ACS patients with a new ELISA-based vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay.

机构信息

Gilles Montalescot, MD, PhD, Bureau 236, Institut de Cardiologie,, Pitié-Salpêtrière University Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France, Tel: +33 142163006, Fax: +33 142162931, E-mail:

出版信息

Thromb Haemost. 2013 Nov;110(5):1055-64. doi: 10.1160/TH13-03-0203. Epub 2013 Aug 8.

Abstract

A new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.

摘要

一种新的 ELISA 技术已经被开发出来,用于测量氯吡格雷治疗患者的血管扩张刺激磷酸蛋白(VASP)血小板反应指数(PRI)。该技术尚未在急性冠脉综合征(ACS)患者或普拉格雷治疗患者中进行评估。我们评估了 ELISA-VASP 在识别 ACS 患者中的高治疗血小板反应性(HPR)方面的准确性,与已建立的血小板功能测试进行比较。使用流式细胞术(FC-VASP)和 ELISA-VASP 技术、光传输聚集测定法(LTA)和 VerifyNow-P2Y12 测定法(VN-P2Y12)测量了 240 例接受氯吡格雷(75 或 150mg)或普拉格雷(5 或 10mg)治疗的 ACS 患者的血小板反应性。当使用 ELISA-VASP PRI 时,整体 ACS 人群中 HPR 患者的比例为 15.5%,其中氯吡格雷治疗患者的比例为 27%,普拉格雷治疗患者的比例为 4%。ELISA-VASP PRI 与 FC-VASP PRI 之间存在很强的相关性(r = 0.83,r2 = 0.68 p < 0.0001),用接收者操作特征(ROC)曲线下面积来识别 HPR(FC-VASP > 50% 的 VASP-PRI)的曲线下面积为 0.94,p < 0.0001。与 FC-VASP、LTA 或 VN-P2Y12 检测相比,ELISA-VASP PRI 的 60% 阈值为识别 HPR 的患者提供了最佳的准确性(似然比= 23.67)。总之,ELISA-VASP 是一种快速、易于使用且特异性强的测试方法,可用于识别噻吩吡啶类药物治疗的 ACS 患者中的 HPR。60% 的阈值值显示出识别这些患者中 HPR 的最佳准确性。

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