platelet aggregation

Definition

Target type: biologicalprocess

The adhesion of one platelet to one or more other platelets via adhesion molecules. [GOC:BHF, GOC:vk]

Platelet aggregation is a crucial process in hemostasis, the body's natural response to bleeding. It involves a complex interplay of cellular signaling, adhesion molecules, and secreted factors that culminate in the formation of a stable platelet plug, effectively sealing off the damaged blood vessel.

The process initiates with vascular injury, exposing the subendothelial collagen beneath the vessel's lining. Platelets, circulating anucleate cells in the blood, bind to collagen through von Willebrand factor (VWF), a protein mediating adhesion. This binding triggers platelet activation, a cascade of intracellular events leading to shape change and the release of granular contents.

Activated platelets express adhesive receptors, such as the glycoprotein (GP) Ib-IX-V complex, which bind to VWF, further strengthening adhesion. They also release adenosine diphosphate (ADP) and thromboxane A2 (TXA2), potent vasoconstrictors that constrict the injured vessel, limiting blood flow.

ADP and TXA2 activate neighboring platelets through G protein-coupled receptors, initiating a positive feedback loop. This amplifies the aggregation response, recruiting more platelets to the site of injury. Activated platelets also express GPIIb/IIIa receptors, which bind to fibrinogen, a clotting factor, forming bridges between platelets and establishing a stable aggregation network.

The fibrinogen-mediated aggregation is crucial for the formation of a tight platelet plug. This plug seals the injured vessel and prevents further blood loss. Simultaneously, the coagulation cascade is initiated, leading to the generation of thrombin, which converts fibrinogen to fibrin. Fibrin forms a meshwork around the platelet plug, further stabilizing and reinforcing the clot.

Platelet aggregation is tightly regulated to prevent uncontrolled clotting. Inhibitors like prostacyclin (PGI2) and nitric oxide (NO) are produced by endothelial cells, counteracting the aggregation signals and maintaining vascular patency. Additionally, several enzymes, including phosphodiesterase and cyclooxygenase inhibitors, can interfere with the production of ADP and TXA2, respectively, thereby reducing platelet aggregation.

The balance between pro- and anti-aggregation factors is critical for maintaining hemostasis. Dysregulation of platelet aggregation can lead to pathological conditions like thrombosis, the formation of blood clots within a blood vessel, or bleeding disorders, characterized by excessive bleeding.'
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Proteins (21)

Compounds (1,257)