Figure 2.

Schematic representation of effects of aspirin and P2Y₁₂-receptor blockers on platelet pathways. (A) In physiological conditions there is balance between anti-aggregatory and pro-aggregatory influences on the platelet from the prostanoid and P2Y₁₂ pathways. PGI₂ formed by the blood vessel wall is anti-aggregatory through the stimulation of adenylyl cyclase (AC) secondary to activation of platelet PGI₂ receptors (IP receptors). Thromboxane A₂ (TXA₂) produced by the activity of cyclooxygenase (COX) within the platelet is pro-aggregatory, acting through platelet TXA₂ receptors (TP receptors). Activation of TP receptors also promotes the release of ADP from platelets which further drives aggregation. ADP produces its pro-aggregatory effects through activation of platelet ADP receptors (P2Y₁₂ receptors) and inhibition of platelet AC. Activation of P2Y₁₂ receptors drives more production of TXA₂ and more release of ADP. (B) In the presence of aspirin, platelet COX is blocked and the TXA₂ pathway of aggregation abolished. The P2Y₁₂ pathway of platelet activation is unaffected. Overall, there is a lessening of pro-aggregatory drive. There is an accompanying lessening in anti-aggregatory influence, as aspirin will also reduce the production of PGI₂ by the blood vessel wall. (C) In the presence of a blocker of P2Y₁₂ receptors, AC inhibition is lessened and so the anti-aggregatory effects of PGI₂ are enhanced. As the effects of the TXA₂ pathway are amplified through the P2Y₁₂ pathway, the pro-aggregatory effects of TXA₂ are also lessened and TXA₂ production is reduced. (D) When aspirin is added to a P2Y₁₂-receptor blocker, there may be some small additional reduction in pro-aggregatory influences by the complete removal of TXA₂ production; however, there is also a loss of PGI₂ which might lead to an even greater reduction in anti-aggregatory influence