Platelet activation and aggregation pathways

Platelets, or thrombocytes, are anucleated cell fragments that play a central role in hemostasis and the pathophysiology of arterial thrombosis [14, 15]. The platelet activation and aggregation pathways encompass a network of receptors and signaling cascades—including the P2Y12, PAR-1, and GP IIb/IIIa receptors—that respond to vascular injury by promoting platelet adhesion, shape change, and the formation of a hemostatic plug [4, 12]. Pharmacological modulation of these pathways, known as antiplatelet therapy, is a cornerstone in the management of cardiovascular diseases such as acute coronary syndrome, myocardial infarction, and ischemic stroke [1, 3]. Common drugs like aspirin and clopidogrel target specific enzymes or receptors within these pathways to reduce the risk of thrombotic events [7, 8]. However, because these pathways are also essential for normal wound healing, the primary therapeutic challenge is balancing antithrombotic efficacy with the inherent risk of significant bleeding [5, 10].

Other names

Platelet aggregation pathwaysPlatelet activation pathwaysAntiplatelet targetsHemostatic pathwaysThrombocyte activation pathways

Antiplatelet drugs inhibit platelet function through several distinct mechanisms: irreversible inhibition of cyclooxygenase-1 (COX-1) to prevent thromboxane A2 synthesis (e.g., aspirin); antagonism of the P2Y12 adenosine diphosphate (ADP) receptor (e.g., clopidogrel, ticagrelor); blockade of the glycoprotein IIb/IIIa (integrin alpha-IIb/beta-3) receptor to prevent fibrinogen-mediated cross-linking (e.g., abciximab); antagonism of the protease-activated receptor 1 (PAR-1) to block thrombin-mediated activation (e.g., vorapaxar); and inhibition of phosphodiesterase (PDE) to increase intracellular cyclic AMP levels (e.g., dipyridamole, cilostazol) [1, 4, 7, 10].