Asher E, Fefer P, Shechter M, Beigel R, Varon D, Shenkman B, Savion N, Hod H, Matetzky S
Shlomi Matetzky, MD, Heart Institute, Sheba Medical Center, Tel Hashomer 52621, Israel, Tel.: +972 3 6352303, Fax: +972 3 534 3888, E-mail:
Thromb Haemost. 2014 Jul 3;112(1):137-41. doi: 10.1160/TH13-10-0845. Epub 2014 Apr 3.
Prior studies have demonstrated significant individual variability of platelet response to clopidogrel, which affects clinical outcome. In patients with stable coronary artery disease (CAD) smoking, diabetes mellitus, elevated body mass index and renal insufficiency, significantly impact response to clopidogrel. The determinants of platelet response to clopidogrel in patients with acute coronary syndrome are unknown. Adenosine diphosphate (ADP)-induced platelet aggregation (PA), hs C-reactive protein, platelet count and mean platelet volume (MPV) were determined 72 hours post clopidogrel loading in 276 consecutive acute myocardial infarction (AMI) patients. Patients with ADP-platelet aggregation ≥ 70% were considered to be clopidogrel non-responders. Eighty-four patients (30%) were clopidogrel non-responders and 192 (70%) were responders (ADP-induced PA: 81 ± 17% vs 49 ± 17%, respectively, p<0.001). Both study groups were comparable with respect to age, gender, prior cardiovascular history, prior aspirin use and risk factors for CAD, including smoking (42% for both groups) and diabetes mellitus (26% vs 22%, respectively, p=0.4). Responders and non-responders had similar angiographic characteristics, indices of infarct size, and similar hs-CRP (29 ± 34 vs 28 ± 34 mg/l, p=0.7) and creatinine (1.08 ± 0.4 mg% vs 1.07 ± 0.4, p=0.9) levels. On the contrary non-responders had significantly larger mean MPV (9 ± 1.2 fl vs 8 ± 1 fl, respectively, p=0.0018), and when patients were stratified into quartiles based on MPV, ADP-induced PA increased gradually and significantly across the quartiles of MPV (p<0.001). In conclusion, increased MPV associated with platelet activation, predicts non-responsiveness to clopidogrel among patients with acute coronary syndrome.
先前的研究已证明，血小板对氯吡格雷的反应存在显著个体差异，这会影响临床结果。在患有稳定型冠状动脉疾病（CAD）的患者中，吸烟、糖尿病、体重指数升高和肾功能不全对氯吡格雷的反应有显著影响。急性冠状动脉综合征患者中血小板对氯吡格雷反应的决定因素尚不清楚。在276例连续的急性心肌梗死（AMI）患者中，在氯吡格雷负荷后72小时测定二磷酸腺苷（ADP）诱导的血小板聚集（PA）、高敏C反应蛋白、血小板计数和平均血小板体积（MPV）。ADP诱导的血小板聚集≥70%的患者被视为氯吡格雷无反应者。84例患者（30%）为氯吡格雷无反应者，192例（70%）为反应者（ADP诱导的PA分别为81±17%和49±17%，p<0.001）。两个研究组在年龄、性别、既往心血管病史、既往阿司匹林使用情况以及CAD的危险因素（包括吸烟，两组均为42%）和糖尿病（分别为26%和22%，p=0.4）方面具有可比性。反应者和无反应者具有相似的血管造影特征、梗死面积指数，以及相似的高敏C反应蛋白（29±34与28±34mg/l，p=0.7）和肌酐（1.08±0.4mg%与1.07±0.4，p=0.9）水平。相反，无反应者的平均MPV显著更大（分别为9±1.2fl和8±1fl，p=0.0018），并且当根据MPV将患者分层为四分位数时，ADP诱导的PA在MPV四分位数中逐渐且显著增加（p<0.001）。总之，与血小板活化相关的MPV增加可预测急性冠状动脉综合征患者对氯吡格雷无反应。
