Role of platelets in hemostasis and thrombosis

Platelets play a primary role in the formation of the hemostatic plug at sites of vessel wall injury and in formation of thrombotic plug at the sites of atherosclerotic lesions. Platelets circulate as anucleated cells at the periphery of the bloodstream. When continuity of the endothelial layer is disrupted and the underlying matrix is exposed, platelets rapidly adhere to the exposed matrix through an interaction between the glycoprotein (Gp) Ib–IX–V complex on their surface and von Willebrand factor (vWf) in the subendothelium. The high fluid shear stress brought about by vascular constriction also promotes Gp Ib–IX–V–von Willebrand factor interaction. This initial interaction, often called platelet adhesion, sets the stage for other adhesive reactions that allow the platelets to essentially seal the vessel-wall defect.

Following adhesion, platelets are activated by a number of agonists such as adenosine diphosphate (ADP) and collagen present at the sites of vascular injury. These agonists activate platelets by binding to specific receptors on the platelet surface. Occupancy of these receptors leads to a series of downstream events that ultimately increases the intracytoplasmic concentration of calcium ions. Receptors coupled to the G-proteins such asADP, epinephrine, thromboxane A2 (TXA2) and thrombin receptors activate phospholipase Cβ (PLCb), whereas receptors activating via the non-receptor tyrosine kinase pathways such as collagen receptor GpVI preferentially activate phospholipase Cγ (PLCγ). Activation of PLCβ or PLCγ results in the production of the two second messengers: diacylglycerol (DAG) and inositol trisphosphate (IP3).