Loss of P2Y receptor desensitization does not impact hemostasis or thrombosis despite increased platelet reactivity in vitro

The hemostatic plug formation at sites of vascular injury is strongly dependent on rapid platelet activation and integrin-mediated adhesion and aggregation. However, to prevent thrombotic complications, platelet aggregate formation must be a self-limiting process. The second-wave mediator adenosine diphosphate (ADP) activates platelets via Gq-coupled P2Y and Gi-coupled P2Y receptors. After ADP exposure, the P2Y receptor undergoes rapid phosphorylation-induced desensitization, a negative feedback mechanism believed to be critical for limiting thrombus growth.