Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Atherosclerosis. 2009 Dec;207(2):608-13. doi: 10.1016/j.atherosclerosis.2009.05.037. Epub 2009 Jun 18.
Circulating monocyte-platelet aggregates (MPA) are a sensitive marker of in vivo platelet activation and patients with atherosclerotic vascular disease exhibit higher levels of MPA. Clopidogrel has been shown to reduce MPA formation in these patients to a greater extent than aspirin. However, response to clopidogrel and aspirin shows a wide variability, and patients with high on-treatment residual platelet reactivity are at an increased risk for adverse events after coronary stenting. We therefore investigated the association of MPA with on-treatment residual agonists'-inducible platelet aggregation in 125 patients on dual antiplatelet therapy after peripheral, coronary or carotid artery stenting.
MPA were characterized by co-expression of monocyte marker CD14 and platelet-specific markers (CD42b and CD62P) by whole blood flow cytometry. Platelet reactivity was determined by light transmission aggregometry, the VerifyNow P2Y12 and aspirin assays, and the vasodilator-stimulated phosphoprotein phosphorylation assay. Cut-off values for residual platelet reactivity were defined according to quartiles of each assay.
The extent of MPA formation showed no significant differences between patients without and with residual ADP-inducible platelet reactivity, and between individuals without and with residual arachidonic acid (AA)-inducible platelet reactivity. Even patients with combined on-treatment residual ADP- and AA-inducible platelet reactivity did not exhibit significantly higher levels of MPA than patients without any on-treatment residual platelet reactivity.
High on-treatment residual agonists'-inducible platelet reactivity results in less than a 25% increase in circulating MPA, suggesting that MPA formation is largely dependent on other factors.
循环单核细胞-血小板聚集物（MPA）是体内血小板活化的敏感标志物，患有动脉粥样硬化性血管疾病的患者表现出更高水平的 MPA。氯吡格雷已被证明比阿司匹林更能减少这些患者的 MPA 形成。然而，氯吡格雷和阿司匹林的反应表现出很大的可变性，并且治疗后残留血小板反应性高的患者在冠状动脉支架置入后发生不良事件的风险增加。因此，我们研究了外周、冠状动脉或颈动脉支架置入后接受双联抗血小板治疗的 125 例患者中 MPA 与治疗后残留激动剂诱导的血小板聚集之间的关系。
通过全血流式细胞术，用单核细胞标志物 CD14 和血小板特异性标志物（CD42b 和 CD62P）共同表达来描述 MPA。通过光传输聚集度测定法、VerifyNow P2Y12 和阿司匹林测定法以及血管扩张刺激磷蛋白磷酸化测定法测定血小板反应性。根据每个测定的四分位数定义残留血小板反应性的截断值。
在无残留 ADP 诱导的血小板反应性和有残留 ADP 诱导的血小板反应性的患者之间，以及在无残留花生四烯酸（AA）诱导的血小板反应性和有残留 AA 诱导的血小板反应性的个体之间，MPA 形成的程度没有显著差异。即使在联合治疗后残留 ADP 和 AA 诱导的血小板反应性的患者中，也没有比任何治疗后残留血小板反应性的患者表现出更高水平的 MPA。
高治疗后残留激动剂诱导的血小板反应性导致循环 MPA 增加不到 25%，表明 MPA 形成在很大程度上取决于其他因素。
