The hemostatic process. Upon vessel injury, platelets roll and become tethered to the vessel wall by interactions with vWF and collagen (noted as black strands). These interactions cause platelet shape change, and release of ADP from dense granules. The activated platelet also generates thromboxane A₂ (TxA₂). Both ADP and TxA₂ are agonists that cause further platelet activation and accumulation of platelets at the site of injury. Vessel injury also causes exposure of tissue factor, which catalyzes the coagulation response. This response results in the formation of thrombin, which further activates platelets and cleaves fibrinogen to form fibrin. The combination of activated platelets and fibrin at the site of injury forms a stable hemostatic plug that arrests bleeding.

The central role of the P2Y₁₂ receptor in platelet activation. Exposure of platelets to vWF and collagen results in the adhesion of platelets and subsequent release of ADP from dense granules. Similarly, activation of platelets by thrombin or thromboxane A₂ also results in release of ADP. Secreted ADP activates the P2Y₁₂ receptor (as depicted) and the P2Y₁ receptor (not shown). P2Y₁₂ receptor activation likely affects thrombus growth and stability by recruiting platelets to the site of injury, and by potentiating dense granule release, procoagulant activity, and aggregation.

Intracellular signaling events downstream of the P2Y₁ and P2Y₁₂ receptors. ADP binds to the P2Y₁₂ receptor and causes a number of intracellular signaling events downstream of the G_i pathway that contribute to fibrinogen receptor activation and platelet aggregation. The P2Y₁₂ receptor–mediated inhibition of adenylyl cyclase is not directly responsible for fibrinogen receptor activation. Potassium channels and PI3K are also activated by the P2Y₁₂ receptor. Both Rap1b and Akt are signaling mediators that contribute to platelet aggregation and are activated in a PI3K-dependent manner. Other mediators of P2Y₁₂ signaling remain to be elucidated.