platelet aggregation inhibition

Thromboxane A2 (TXA2) produced by activated platelets stimulates activation of new platelets and increases platelet aggregation by mediating expression of GP IIb/IIIa in the cell membrane of platelets.

Circulating fibrinogen binds to GP IIb/IIIa receptors causing aggregation.

Thrombin converts fibrinogen to fibrin which is cross linked by factor XIII to form a clot.

Aspirin inhibits prostaglandin formation which leads to TXA2 inhibition.

Clopidrogel which is a prodrug activated by CYP2C19 irreversitly inhibits P2Y12 and ADP receptors which blocks the activation of GP IIb/IIIa receptors to bind with fibrinogen.

cAMP inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules that would lead to activation of additional platelets and the coagulation cascade.

platelet aggregation

 

Vascular wall injury results in exposure of collagen and subendothelial proteins. Initial platelet adhesion is mediated via VWF binding to the GP Ib/IX/V complex on the platelet surface. Platelets begin to slow down and transiently adhere or roll along the vessel wall. Collagen binding to GPVI results in cellular activation resulting in firm adhesion and spreading through the activated receptors Gp IIb/IIIb and alpha2beta1. Platelet adhesion also results in intracellular signaling and platelet activation resulting in degranulation including release of ADP, generation of thromboxane, activation of the Gp IIb/IIIa complex and exposre of anionic phospholipid and generation of procoagulation microvesicles. These facilitate further local recruitment of platelets into the vicinity resulting in platelet aggregation mediated by fibrinogen and VWF bridging between activated Gp IIb/IIIa on adjacent cells The exposure of anionic phospholipid provides a surface upon which platelets can support thrombin generation and fibrin formation resulting in stabilization of resulting haemostatic plug.

Platelet function analysis

Blood Reviews 2005