Platelet Adhesion and Aggregation

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Animation description: Platelet adhesion and aggregation.
In flowing blood, red cells predominate in the axial stream, while the biconvex disc-shaped platelets are marginated along the vessel wall where they are well-positioned to monitor the integrity of the endothelium. The normal endothelium provides a non-adhesive surface to circulating platelets.
However, when vessel wall injury occurs, for example, by cutting or severing of a vessel, or as shown here, by a puncture, and there is endothelial damage, the initial response of platelets is that of adhesion to collagen fibres in the exposed subendothelium.
Collagen is one of the most thrombogenic components of the subendothelial matrix responsible for the initiation of platelet adhesion. A number of adhesive receptors on the platelet surface membrane interact either directly or indirectly with collagen.
Initial binding of platelets is considered to occur via the integrin α2β1 (GPIa-IIa) receptor, which allows for further binding to collagen via the GPVI receptor, initiating transmembrane and, subsequently, intracellular signalling. Adhesion of platelets to the exposed subendothelium is influenced by shear rates. At high shear, α2β1 and GPVI are not sufficient to initiate binding to collagen, and binding of the GPIb-IX-V receptor to von Willebrand factor -- abbreviated here as V.W.F. -- that is immobilized on collagen, becomes essential in platelet adhesion.
Platelet adhesion at the site of vessel wall damage initiates activation events that result in aggregation. Adherent platelets undergo a dramatic shape change to an irregular sphere with multiple filipodia spreading on the subendothelium increasing their area of surface contact.
Adherent platelets also secrete or release the contents of their storage granules - the alpha and dense granules -- by an exocytic process. This provides a high local concentration of effector molecules essential for platelet plug formation at the site of vascular injury. For example, the aggregating agent A.D.P. is released from the dense granules.
Platelet activation stimulates the formation of another aggregating agent, thromboxane A2 -- abbreviated here as T.X.A2 -- via the arachidonic acid cascade -- details are shown in Figure 26-5.
A.D.P., thromboxane A2 and thrombin bind to specific platelet membrane receptors -- details are shown in Table 26-1 -- and stimulate aggregation on and around the platelets adherent to the subendothelium via receptor-mediated signal transduction events. Aggregation is an active metabolic process: binding of any of the agonists to their respective membrane receptors initiates signalling pathways that ultimately convert integrin αIIbβ3 -- or GPIIb-IIIa - from a low affinity resting state to a high-affinity activated state for binding extracellular soluble ligands such as plasma fibrinogen and von Willebrand factor -- fibrinogen is shown here.
The transmission of an intracellular signal leads to disruption of the complex between the cytoplasmic tails of αIIbβ3, followed by a conformational change in its extracellular globular head domains from a bent to an extended state, promoting the binding to fibrinogen and von Willebrand factor.
Divalent fibrinogen and multivalent von Willebrand factor function as bridges between αIIbβ3 receptors on adjacent activated platelets, thus allowing platelet aggregation to proceed.
In this way, the large and complex metabolic repertoire of platelets allows them to effectively perform their primary physiological role, that of supporting hemostasis upon tissue trauma to form a platelet plug that arrests blood loss from a vascular injury.
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