Platelets play a major role in hemostasis, and alterations in platelet mechanisms may lead to a bleeding diathesis. When the blood vessel is injured, 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) (Fig. 44.1). Adhesion is followed by recruitment of additional platelets which form clumps, a process called aggregation (cohesion). This involves binding of fibrinogen to specific platelet surface receptors, a complex composed of glycoproteins IIb–IIIa (GPIIb–IIIa). 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 coagulation mechanisms; several key enzymatic reactions occur on the platelet membrane lipoprotein surface. A number of physiological agonists interact with specific receptors on platelet surface to induce responses including a change in platelet shape from discoid to spherical (shape change), aggregation, secretion, and thromboxane A2 (TxA2) production. Other agonists, such as prostacyclin, inhibit these responses. Ligation of the platelet receptors initiates the production or release of several intracellular messenger molecules including Ca2+ ions, products of phosphoinositide (PI) hydrolysis by phospholipase C (diacylglycerol, DG, and inositol 1, 4, 5-triphosphate, InsP3), TxA2 and cyclic nucleotides (cAMP) (Fig. 44.1). These induce or modulate the various platelet responses of Ca2+ mobilization, protein phosphorylation, aggregation, secretion and liberation of arachidonic acid.