ADP is a key platelet agonist responsible for platelet aggregation and thrombus stability in vivo. Our recent finding indicated that ADP stimulation initiates a PI3K-dependent signaling, which regulates the cleavage of integrin αIIbβ3-associated prothrombin, leading to a quick thrombin generation. Thrombin then activates protease-activated receptor-1 (PAR-1) and mediates dense granule secretion and second wave of platelet aggregation. This finding identified a previous unrecognized mechanism which is indispensable to relay the platelet activation process induced by ADP. The study was published online inthe Journal of Thrombosis and Haemostasis.