Department of Cardiology, University of Ioannina Medical School, 45110 Ioannina, Greece.
Platelets. 2012;23(2):121-31. doi: 10.3109/09537104.2011.597527. Epub 2011 Aug 2.
Platelets are involved in thrombus formation and inflammation following vascular injury, while clopidogrel exerts antithrombotic and anti-inflammatory actions. We investigated various platelet-derived prothrombotic and proinflammatory mediators as well as the platelet aggregatory response in patients with acute coronary syndromes (ACS) receiving clopidogrel, as a function of the patient responsiveness to drug treatment. Blood samples were obtained from 40 patients with recent (<24 h) ACS before clopidogrel loading 600 mg (followed by a maintenance dose of 75 mg/day) as well as 5-days and 30-days afterwards. Twelve patients exhibited platelet reactivity index (PRI) values higher than 50% evaluated by the Vasodilator Stimulated Phosphoprotein (VASP) test at 5 days and were characterized as nonresponders. The platelet response to adenosine diphosphate (ADP) and thrombin receptor agonist peptide-14 (TRAP) was studied by flow cytometry and light transmission aggregometry. A maximum reduction of ADP- or TRAP-induced platelet aggregation in 28 clopidogrel responding patients was observed at 5 days postclopidogrel loading, whereas in nonresponders, it was achieved at 30-days along with a significant decrease in the PRI values. Similar results were obtained for the membrane expression of CD40L and the production of platelet-derived microparticles. By contrast, the maximum inhibition of P-selectin expression and platelet-leukocyte conjugate formation was observed at 30-days in both patient groups. A maintenance dose of 75 mg clopidogrel differentially affects the platelet aggregation and platelet-derived prothrombotic and proinflammatory mediators in ACS patients within the first month of the treatment, a phenomenon that is highly influenced by the drug response variability. Since these factors may be involved in the major adverse cardiovascular events in ACS patients, especially in those undergoing percutaneous coronary intervention, the above findings may be clinically important.
血小板参与血管损伤后的血栓形成和炎症反应，而氯吡格雷则具有抗血栓和抗炎作用。我们研究了急性冠脉综合征（ACS）患者在接受氯吡格雷治疗时，各种血小板衍生的促血栓形成和促炎介质以及血小板聚集反应，这些反应与患者对药物治疗的反应有关。从最近（<24 小时）发生 ACS 的 40 名患者中采集血液样本，这些患者在接受氯吡格雷负荷量 600mg 治疗（随后维持剂量为 75mg/天）之前、5 天和 30 天后采集。通过 Vasodilator Stimulated Phosphoprotein（VASP）测试评估，在 5 天时，有 12 名患者的血小板反应指数（PRI）值高于 50%，被认为是无反应者。通过流式细胞术和透光比浊法研究了对二磷酸腺苷（ADP）和血栓素受体激动肽-14（TRAP）的血小板反应。在 28 名氯吡格雷反应患者中，在氯吡格雷负荷后 5 天观察到 ADP 或 TRAP 诱导的血小板聚集最大减少，而在无反应者中，在 30 天达到最大减少，同时 PRI 值显著降低。CD40L 的膜表达和血小板衍生的微颗粒的产生也得到了类似的结果。相比之下，在两组患者中，P-选择素表达和血小板-白细胞结合的最大抑制作用是在 30 天观察到的。ACS 患者在治疗的第一个月内，75mg 氯吡格雷的维持剂量会对血小板聚集和血小板衍生的促血栓形成和促炎介质产生不同的影响，这种现象受药物反应变异性的影响很大。由于这些因素可能与 ACS 患者的主要不良心血管事件有关，尤其是那些接受经皮冠状动脉介入治疗的患者，因此上述发现可能具有临床意义。
