Abstract
Discovered in the 1980s, the procoagulant function of platelets is due to their inherent ability to provide, following activation, a critical platform at their plasma membrane surface for the activation of blood clotting enzyme complexes to generate thrombin. Upon platelet activation, the asymmetric orientation of membrane phospholipids rapidly collapses resulting in a calcium-dependent exposure of the anionic phospholipid, phosphatidylserine (PS), at the outer platelet surface. Binding of blood clotting enzyme complexes to this procoagulant membrane surface allows a dramatic increase in the rate of conversion of zymogens to active serine proteases and in turn the production of a burst of thrombin leading to fibrin clot formation and to further platelet activation. The energy-independent, calcium-dependent, platelet scramblase activity, which governs the bidirectional exchange of phospholipids between the two leaflets of the bilayer, is essential for PS exposure during platelet activation. The platelet scramblase protein has remained elusive for years until a significant advance was recently made with the identification of TMEM16F, a membrane protein essential for calcium-dependent PS exposure with loss-of-function mutations in Scott syndrome, a bleeding disorder due to an impaired platelet procoagulant activity.
Platelets also have the capacity to interfere with the fibrinolytic system in several ways, and so doing they can modulate the outcome of thrombolytic therapy by delaying reperfusion and mediating reocclusion but also by promoting bleeding complications. Remarkably, a rare autosomal dominant bleeding disorder, the Quebec platelet disorder, is a unique gain-of-function defect in fibrinolysis.
The most clinically relevant aspects of these two platelet functions will be discussed in this chapter.
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Payrastre, B., Alessi, MC., SiƩ, P. (2017). Alterations of the Platelet Procoagulant or Fibrinolytic Functions. In: Gresele, P., Kleiman, N., Lopez, J., Page, C. (eds) Platelets in Thrombotic and Non-Thrombotic Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-47462-5_63
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