The William Harvey Research Institute, Barts & the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.
J Thromb Haemost. 2011 Mar;9(3):552-61. doi: 10.1111/j.1538-7836.2010.04160.x.
Aspirin and antagonists of platelet ADP P2Y(12) receptors are often coprescribed for protection against thrombotic events. However, blockade of platelet P2Y(12) receptors can inhibit thromboxane A(2) (TXA(2))-dependent pathways of platelet activation independently of aspirin.
To assess in vitro whether aspirin adds additional antiaggregatory effects to strong P2Y(12) receptor blockade.
With the use of platelet-rich plasma from healthy volunteers, determinations were made in 96-well plates of platelet aggregation, TXA(2) production and ADP/ATP release caused by ADP, arachidonic acid, collagen, epinephrine, TRAP-6 amide and U46619 (six concentrations of each) in the presence of prasugrel active metabolite (PAM; 0.1-10 μmol L(-1)), aspirin (30 μmol L(-1)), PAM + aspirin or vehicle. results: PAM concentration-dependently inhibited aggregation; for example, aggregation in response to all concentrations of ADP and U46619 was inhibited by ≥ 95% by PAM at > 3 μmol L(-1) . In further tests of PAM (3 μmol L(-1)), aspirin (30 μmol L(-1)) and PAM + aspirin, aspirin generally failed to produce more inhibition than PAM or additional inhibition to that caused by PAM. The antiaggregatory effects of PAM were associated with reductions in the platelet release of both TXA(2) and ATP + ADP. Similar effects were found when either citrate or lepirudin were used as anticoagulants, and when traditional light transmission aggregometry was conducted at low stirring speeds.
P2Y(12) receptors are critical to the generation of irreversible aggregation through the TXA(2) -dependent pathway. As a result, strong P2Y(12) receptor blockade alone causes inhibition of platelet aggregation that is little enhanced by aspirin. The clinical relevance of these observations remains to be determined.
阿司匹林和血小板 ADP P2Y(12)受体拮抗剂常联合用于预防血栓事件。然而，血小板 P2Y(12)受体的阻断可独立于阿司匹林抑制血小板激活的血栓素 A(2) (TXA(2))依赖途径。
评估体外阿司匹林是否可增强强 P2Y(12)受体阻断剂的抗聚集作用。
使用来自健康志愿者的富含血小板血浆，在 96 孔板中测定 ADP、花生四烯酸、胶原、肾上腺素、TRAP-6 酰胺和 U46619（每种物质六个浓度）引起的血小板聚集、TXA(2)生成和 ADP/ATP 释放，分别在普拉格雷活性代谢物 (PAM；0.1-10 μmol L(-1))、阿司匹林（30 μmol L(-1))、PAM +阿司匹林或载体存在下进行。结果：PAM 浓度依赖性地抑制聚集；例如，在 > 3 μmol L(-1) 时，PAM 以 ≥ 95%的程度抑制了所有浓度的 ADP 和 U46619 引起的聚集。在 PAM (3 μmol L(-1))、阿司匹林（30 μmol L(-1))和 PAM +阿司匹林的进一步测试中，阿司匹林通常未能产生比 PAM 更多的抑制作用，也未能对 PAM 引起的抑制作用产生额外的抑制作用。PAM 的抗聚集作用与血小板 TXA(2)和 ATP + ADP 释放的减少有关。当使用柠檬酸盐或 lepirudin 作为抗凝剂或在低搅拌速度下进行传统的光传输聚集测定时，也发现了类似的作用。
P2Y(12)受体对于通过 TXA(2)依赖途径产生不可逆聚集至关重要。因此，单独使用强 P2Y(12)受体阻断剂即可引起血小板聚集的抑制，阿司匹林对其的增强作用很小。这些观察结果的临床相关性仍有待确定。
