Platelet biology and functions: new concepts and clinical perspectives

Platelets — blood cells continuously produced from megakaryocytes mainly in the bone marrow — are implicated not only in haemostasis and arterial thrombosis, but also in other physiological and pathophysiological processes. This Review describes current evidence for the heterogeneity in platelet structure, age, and activation properties, with consequences for a diversity of platelet functions. Signalling processes of platelet populations involved in thrombus formation with ongoing coagulation are well understood. Genetic approaches have provided information on multiple genes related to normal haemostasis, such as those encoding receptors and signalling or secretory proteins, that determine platelet count and/or responsiveness. As highly responsive and secretory cells, platelets can alter the environment through the release of growth factors, chemokines, coagulant factors, RNA species, and extracellular vesicles. Conversely, platelets will also adapt to their environment. In disease states, platelets can be positively primed to reach a pre-activated condition. At the inflamed vessel wall, platelets interact with leukocytes and the coagulation system, interactions mediating thromboinflammation. With current antiplatelet therapies invariably causing bleeding as an undesired adverse effect, novel therapies can be more beneficial if directed against specific platelet responses, populations, interactions, or priming conditions. On the basis of these novel concepts and processes, we discuss several initiatives to target platelets therapeutically. This Review provides an update of the latest developments in our understanding of platelet functions and populations in normal physiology and in haemorrhagic, thrombotic, and inflammatory conditions. These advancements can aid in tailoring new strategies to target platelets in disease states while avoiding the increased risk of bleeding associated with current antiplatelet therapies. Multiomic approaches combined with functional testing of platelets have greatly advanced the understanding of genetic factors of platelet-related haemorrhagic disorders, but to a lesser extent the understanding of the causes of platelet hyper-reactivity.Negative and positive platelet priming alter the threshold for platelet activation in the circulation, with consequences for diagnostic assays.The diverse pathways of information transfer by platelets through release of bioactive molecules and extracellular vesicles are still incompletely understood.Platelets contribute to thromboinflammatory processes by their capacity to interact functionally with the activated endothelium, leukocytes, and coagulation proteins; the mechanisms are multivariate.Platelet populations and specific platelet responses are promising targets for new antithrombotic treatment of patients with cardiovascular disease. Multiomic approaches combined with functional testing of platelets have greatly advanced the understanding of genetic factors of platelet-related haemorrhagic disorders, but to a lesser extent the understanding of the causes of platelet hyper-reactivity. Negative and positive platelet priming alter the threshold for platelet activation in the circulation, with consequences for diagnostic assays. The diverse pathways of information transfer by platelets through release of bioactive molecules and extracellular vesicles are still incompletely understood. Platelets contribute to thromboinflammatory processes by their capacity to interact functionally with the activated endothelium, leukocytes, and coagulation proteins; the mechanisms are multivariate. Platelet populations and specific platelet responses are promising targets for new antithrombotic treatment of patients with cardiovascular disease.