Farrell T P, Hayes K B, Sobel B E, Schneider D J
Department of Medicine, The University of Vermont College of Medicine, Burlington, USA.
Am J Cardiol. 1999 Mar 1;83(5):770-4. doi: 10.1016/s0002-9149(98)00987-4.
A decreased threshold for platelet activation apparently contributes to the risk of cardiovascular events, such as acute myocardial infarction. To evaluate the impact of specific agents, we characterized platelet reactivity in 9 healthy subjects before and after 5 days of ingestion of 4 commonly prescribed regimens, 81 mg of aspirin daily, 325 mg of aspirin daily, ticlopidine 250 mg twice daily, and ticlopidine plus 325 mg of aspirin daily. Platelet reactivity was assessed with (1) aggregometry induced by 4 microM adenosine diphosphate (ADP) and collagen (0.19 mg/ml) and performed in platelet-rich plasma; and (2) flow cytometric determination of ADP-induced (0.2, 0.8, and 1.5 microM) P-selectin expression in whole blood. Because anticoagulants alter platelet reactivity, results were obtained with 3 anticoagulants, citrate, enoxaparin, or corn trypsin inhibitor (CTI, a specific inhibitor of factor XIIa without effect on other coagulation factors). Ingestion of aspirin did not alter platelet activation as assessed with flow cytometry. Inhibition of the second phase of aggregation was seen with ADP-induced aggregation in platelet-rich plasma anticoagulated with citrate but not enoxaparin or CTI. Ingestion of ticlopidine led to inhibition of ADP-induced aggregation and P-selectin expression. Inhibition of platelet reactivity after the combination of aspirin and ticlopidine did not differ from ticlopidine alone. Marked interindividual variability in platelet reactivity was seen after ingestion of ticlopidine. The results indicate that assessment of effects of specific pharmacologic regimens with accurate and readily available assays of platelet reactivity may facilitate effective prophylaxis and treatment of high-risk subjects with antiplatelet regimens designed to optimally diminish platelet reactivity.
血小板激活阈值降低显然会增加心血管事件的风险，如急性心肌梗死。为了评估特定药物的影响，我们对9名健康受试者在摄入4种常用处方方案（每日81毫克阿司匹林、每日325毫克阿司匹林、每日两次250毫克噻氯匹定、每日噻氯匹定加325毫克阿司匹林）5天前后的血小板反应性进行了表征。血小板反应性通过以下方法评估：（1）在富含血小板血浆中，用4微摩尔二磷酸腺苷（ADP）和胶原蛋白（0.19毫克/毫升）诱导的凝集试验；（2）流式细胞术测定全血中ADP诱导（0.2、0.8和1.5微摩尔）的P-选择素表达。由于抗凝剂会改变血小板反应性，因此使用3种抗凝剂（柠檬酸盐、依诺肝素或玉米胰蛋白酶抑制剂（CTI，一种特异性因子XIIa抑制剂，对其他凝血因子无影响））获得了结果。用流式细胞术评估，摄入阿司匹林并未改变血小板激活。在用柠檬酸盐抗凝的富含血小板血浆中，ADP诱导的凝集可见第二阶段的抑制，但依诺肝素或CTI抗凝的血浆中未见。摄入噻氯匹定导致ADP诱导的凝集和P-选择素表达受到抑制。阿司匹林和噻氯匹定联合使用后对血小板反应性的抑制与单独使用噻氯匹定没有差异。摄入噻氯匹定后，个体间血小板反应性存在明显差异。结果表明，用准确且易于获得的血小板反应性检测方法评估特定药物方案的效果，可能有助于对高危受试者进行有效的预防和治疗，采用旨在最佳降低血小板反应性的抗血小板方案。
