BACKGROUND: 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. OBJECTIVES: To assess in vitro whether aspirin adds additional antiaggregatory effects to strong P2Y(12) receptor blockade. METHODS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVES: To assess in vitro whether aspirin adds additional antiaggregatory effects to strong P2Y(12) receptor blockade. METHODS: 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. CONCLUSIONS: 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.
Authors: S K Yao; J C Ober; J McNatt; C R Benedict; M Rosolowsky; H V Anderson; K Cui; J P Maffrand; W B Campbell; L M Buja Journal: Circ Res Date: 1992-01 Impact factor: 17.367
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Authors: Dorothee Kaudewitz; Philipp Skroblin; Lukas H Bender; Temo Barwari; Peter Willeit; Raimund Pechlaner; Nicholas P Sunderland; Karin Willeit; Allison C Morton; Paul C Armstrong; Melissa V Chan; Ruifang Lu; Xiaoke Yin; Filipe Gracio; Katarzyna Dudek; Sarah R Langley; Anna Zampetaki; Emanuele de Rinaldis; Shu Ye; Timothy D Warner; Alka Saxena; Stefan Kiechl; Robert F Storey; Manuel Mayr Journal: Circ Res Date: 2015-12-08 Impact factor: 17.367