Molecular Mechanisms of Platelet Activation and Inhibition

Abstract

The basic mechanisms that operate in hemostasis and thrombosis are similar although the inciting processes and the consequences are different. Both encompass a complex sequence of interrelated events involving the vessel wall, platelets, and the coagulation system. Following injury to the blood vessel, platelets adhere to exposed subendothelium by a process (adhesion) which involves the interaction of a plasma protein, von Willebrand factor (vWF), and a specific protein on the platelet surface, glycoprotein Ib (GPIb). Adhesion is followed by recruitment of additional platelets which form clumps, a process called aggregation (cohesion). This platelet-platelet interaction involves binding of fibrinogen to specific platelet surface receptors - a complex comprised of glycoproteins IIb-IIIa (GPIIb-IIIa). In the resting state, platelets do not bind fibrinogen; platelet activation induces a conformational change in the GPIIb-IIIa complexes leading to fibrinogen binding and a sequence of events resulting in aggregation. Activated platelets release contents of their granules (secretion or release reaction), such as adenosine diphosphate (ADP) and serotonin from the dense granules, which cause recruitment of additional platelets. In addition, platelets play a major role in hemostasis and thrombosis by contributing to coagulation mechanisms; several key enzymatic reactions in blood coagulation occur on the platelet membrane lipoprotein surface. Thrombin generation and formation of a clot composed of blood cells and fibrin strands leads to restoration of hemostasis or thrombosis with its attendant sequalae.