Platelets and Their Disorders

Platelets play a key role in haemostasis, inflammation and cancer biology. They show specific structural elements, including invaginations of the plasma membrane, a network of residual smooth endoplasmic reticulum, a highly specialized cytoskeleton maintaining the discoid structure of platelets and several kinds of organelles. Stimulation occurs by adhesion of platelets to sub-endothelial matrix proteins, through the action of specific adhesion-signalling receptors; soluble agonists (including ADP, thrombin, thromboxane A2) act as amplifiers of activation. A series of reactions (collectively forming the ‘outside-in signalling’) triggers platelet spreading, granule secretion, aggregation and clot retraction. Defects in these complex signalling networks determine inherited or acquired platelet disorders, mainly characterized by altered haemostasis. Nowadays, genomic and post-genomic techniques allow better identification and classification of platelet-related diseases. Key Concepts Platelets are anucleated cells playing a crucial role in haemostasis and thrombosis, as well as in innate immunity, angiogenesis and cancer promotion. Platelet activation is a complex signalling network encompassing the response to multiple agonists and acting via interactions among several molecules (including integrins, G-protein-coupled receptors, protein kinases and phospholipases). Ultrastructural studies and omics approaches are ideal ways to investigate platelet sub-cellular compartments and signalling pathways, playing a fundamental role in the pathogenesis of several pathologies. The recent identification of specific sub-network defects in inherited platelet disorders will lead to understanding of the correlation between signal transduction pathways and cell functions. The identification of specific sub-network defects in inherited platelet disorders will allow better classification of platelet-related diseases. Keywords: platelets; signalling networks; platelet disorders; cytoskeleton; secretory granules