Tsoumani Maria E, Tatsidou Prokopia T, Ntalas Ioannis V, Goudevenos John A, Tselepis Alexandros D
a Department of Chemistry, Laboratory of Biochemistry, School of Medicine , University of Ioannina , Ioannina , Greece.
b Department of Cardiology, School of Medicine , University of Ioannina , Ioannina , Greece.
Platelets. 2016 Dec;27(8):812-820. doi: 10.1080/09537104.2016.1192113. Epub 2016 Jun 23.
Platelet adhesion and aggregation are key functions leading to thrombus formation. The effect of aspirin, clopidogrel, and ticagrelor on platelet aggregation has been well established, however, there is limited data on the effect of these drugs on platelet adhesion. We therefore evaluated the effect of these drugs on platelet adhesion in acute coronary syndrome (ACS) patients. Citrated blood was collected from 50 ACS patients loaded with 325 mg of aspirin (baseline) and at 5 days after the administration of aspirin 100 mg/day and clopidogrel (600 mg loading dose, 75 mg/day) (n = 26) or ticagrelor (180 mg loading dose, 90 mg × 2/day) (n = 24). High on-treatment platelet reactivity (HTPR) to clopidogrel was estimated by vasodilator stimulated phosphoprotein (VASP) phosphorylation assay. Platelet adhesion to collagen was studied for 6 min under high shear stress and was evaluated using the time to platelet recruitment (TPR), the perimeter and average area of each adherent object, number of adherent objects, and the total percent of surface coverage (SC%). Six ACS patients exhibited HTPR to clopidogrel and excluded from the platelet adhesion assays. TPR and SC% values were similar among patient groups at baseline and controls. However, all other adhesion parameters were different in ACS patients, indicating the formation of more aggregates in regard to controls. At 5 days post-treatment with either clopidogrel or ticagrelor, the TPR values were increased and the SC% values were reduced to a similar extent compared with baseline. However, significant differences were observed in the ticagrelor group in the perimeter, number of adherent objects, and the average area of each adherent object indicating a more potent inhibition of adherence-induced platelet aggregation than clopidogrel. In conclusion, aspirin does not affect platelet adherence to collagen, whereas clopidogrel and ticagrelor inhibit to a similar extent dynamic platelet adhesion at 5 days post-treatment in ACS patients. However, ticagrelor exhibits a greater inhibitory effect on reducing adhesion-induced platelet aggregation.
血小板黏附和聚集是导致血栓形成的关键功能。阿司匹林、氯吡格雷和替格瑞洛对血小板聚集的作用已得到充分证实,然而,关于这些药物对血小板黏附作用的数据有限。因此,我们评估了这些药物对急性冠状动脉综合征(ACS)患者血小板黏附的影响。从50例服用325mg阿司匹林(基线)的ACS患者中采集枸橼酸盐抗凝血,在给予阿司匹林100mg/天和氯吡格雷(负荷剂量600mg,75mg/天)(n = 26)或替格瑞洛(负荷剂量180mg,90mg×2/天)(n = 24)5天后再次采集。通过血管扩张剂刺激磷蛋白(VASP)磷酸化试验评估氯吡格雷治疗时的高血小板反应性(HTPR)。在高剪切应力下研究血小板与胶原蛋白的黏附6分钟,并使用血小板募集时间(TPR)、每个黏附物体的周长和平均面积、黏附物体数量以及表面覆盖总面积百分比(SC%)进行评估。6例对氯吡格雷表现出HTPR的ACS患者被排除在血小板黏附试验之外。基线时患者组和对照组的TPR和SC%值相似。然而,ACS患者的所有其他黏附参数均不同,表明与对照组相比形成了更多聚集体。在氯吡格雷或替格瑞洛治疗5天后与基线相比,TPR值增加,SC%值降低到相似程度。然而,替格瑞洛组在周长、黏附物体数量和每个黏附物体的平均面积方面观察到显著差异,表明其对黏附诱导的血小板聚集的抑制作用比氯吡格雷更强。总之,阿司匹林不影响血小板与胶原蛋白的黏附,而氯吡格雷和替格瑞洛在ACS患者治疗5天后对动态血小板黏附的抑制程度相似。然而,替格瑞洛在减少黏附诱导的血小板聚集方面表现出更大的抑制作用。