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27/03/2025, 20:10:55

    Platelet adhesion, activation, and aggregation


    At a site of endothelial injury platelets a recruited to form the “platelet plug”. This process is taught, and commonly referred to, as primary haemostasis

    Damage to vascular endothelium exposes the underlying extracellular matrix to the intravascular space; these underlying proteins are thrombogenic and trigger numerous haemostatic processes.

    Platelet adhesion

    A nascent thrombocyte in circulation binds exposed collagen through the glycoprotein Ia/IIa complex (integrin ɑ2β1). This adhesion is also facilitated by the von Willebrand factor which binds collagen and also binds platelets; This interaction is probably dealt with by different receptors. One of these is glycoprotein Ib. I resign myself to expanding this later…

    Platelet activation

    Adhesion of platelets would seem to be the basis of formation of the platelet plug. However, platelets that are adhered, or near the site of raw subendothelium must be activated to fulfil their true potential. This is mediated by many agonists-receptor interactions, most of which are far beyond the grasp of the author. There is talk of strong and weak agonists, with the strong including collagen and thrombin and the weak ADP. One receptor with particular clinical significance, though, is the glycoprotein IIa/IIIb complex because it is the target for abciximab. Another is the P2Y12 adenosine diphosphate receptor (see P2Y ADP receptors) which is the target of ticagrelor, clopidogrel, and prasugrel.

    Returning form the weeds, binding of the various platelet receptors to their ligands activates platelets through the infamous cyclic adenosine monophosphate signalling pathway.

    Activation leads to shape change and degranulation. A key event is the resulting increase in intracellular calcium with leads to the complexing of glycoproteins IIa and IIIb to form the activated glycoprotein IIa/IIIb complex which binds fibrinogen and plays an important role in aggregation. The IIa/IIIb complex also weakly binds von Willebrand.

    Platelet aggregation

    At the site of injury, the adhered and activated platelets can now bind fibrinogen. The glycoprotein IIa/IIIb complex facilitates this and promotes firm aggregation of the platelet plug in a vessel through which blood is flowing. We have now the makings of a clot and the production of activated clotting factor through the coagulation cascade crosslinks the bound fibrin and closes of the offending injury.

    Of course, none of this is sequential…

    Various coagulation factors are also doing their work from the moment of exposure of the thrombogenic extracellular matrix. Thrombin is a strong agonist of platelet activation and its concentration rises at the site of insult due to failure of the endothelial mechanisms of local anticoagulation. Thrombomodulin, so deftly named, is a tireless workhorse until its synthesis is arrested when the endothelium that produces it is scratched off the basal lamina.

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