Dropinski Jerzy, Jakiela Bogdan, Sanak Marek, Wegrzyn Wojciech, Biernat Marta, Dziedzina Sylwia, Plutecka Hanna, Szczeklik Andrew
Department of Medicine, Jagiellonian University, ul. Skawinska 8, 31-066 Krakow, Poland.
Thromb Haemost. 2007 Jul;98(1):201-9.
We searched for additional anti-platelet effects of clopidogrel in coronary artery disease (CAD) patients treated with aspirin. Response to clopidogrel was also stratified according to aspirin resistance. Out of 76 screened aspirin-treated CAD male patients, five were aspirin-resistant based on arachidonic acid (AA) and ADP aggregometry. These five patients and 15 aspirin-sensitive patients entered the proper study. Platelet function was assessed at baseline and after one week of additional clopidogrel treatment using aggregometry, flow cytometry (ADP, TRAP-6) and platelet reactivity index (PRI) based on VASP (vasodilatorstimulated phosphoprotein) expression. We evaluated the same markers in 15 healthy men after aspirin treatment. In healthy subjects aspirin did not affect resting or ADP-induced activated GPIIb/IIIa and P-selectin expression. The P-selectin expression on ADP-activated platelets was increased (p < 0.01) in aspirin treated ASA-resistant CAD patients as compared to ASA-sensitive group or aspirin-treated healthy subjects. Clopidogrel significantly decreased ADP and AA-induced platelet aggregation and overcame aspirin resistance in four of five patients. Expression of ADP-induced activation markers was significantly lowered after clopidogrel in all patients. Out of 20 patients, five did not respond to clopidogrel (<10% inhibition of ADP aggregation), and this group showed no change in expression of ADP-induced activation markers after clopidogrel. Clopidogrel treatment significantly reduced PRI only in the clopidogrel-sensitive group. In conclusion, the addition of clopidogrel to aspirin provides greater inhibition of platelets and can overcome aspirin resistance. Flow cytometric analysis of platelets is useful for monitoring of clopidogrel therapy.
我们在接受阿司匹林治疗的冠状动脉疾病（CAD）患者中探寻氯吡格雷的额外抗血小板作用。根据阿司匹林抵抗情况，对氯吡格雷的反应也进行了分层。在76名接受筛查的服用阿司匹林的CAD男性患者中，基于花生四烯酸（AA）和ADP聚集试验，有5名患者存在阿司匹林抵抗。这5名患者和15名阿司匹林敏感患者进入了相应研究。在基线以及氯吡格雷额外治疗一周后，使用聚集试验、流式细胞术（ADP、TRAP - 6）以及基于血管舒张刺激磷蛋白（VASP）表达的血小板反应指数（PRI）评估血小板功能。我们在15名健康男性服用阿司匹林后评估了相同的标志物。在健康受试者中，阿司匹林不影响静息状态或ADP诱导的活化GPIIb/IIIa及P - 选择素表达。与阿司匹林敏感组或服用阿司匹林的健康受试者相比，服用阿司匹林的阿司匹林抵抗CAD患者中，ADP激活血小板上的P - 选择素表达增加（p < 0.01）。氯吡格雷显著降低ADP和AA诱导的血小板聚集，并使5名患者中的4名克服了阿司匹林抵抗。在所有患者中，氯吡格雷治疗后ADP诱导的活化标志物表达显著降低。在20名患者中，有5名对氯吡格雷无反应（ADP聚集抑制<10%），该组在氯吡格雷治疗后ADP诱导的活化标志物表达无变化。氯吡格雷治疗仅在氯吡格雷敏感组显著降低了PRI。总之，在阿司匹林基础上加用氯吡格雷可提供更强的血小板抑制作用，并能克服阿司匹林抵抗。血小板的流式细胞术分析有助于监测氯吡格雷治疗。
