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ABSTRACT 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. KEY POINTS * 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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PLATELETS AND DISEASES: SIGNAL TRANSDUCTION AND ADVANCES IN TARGETED THERAPY Article Open

access 16 May 2025 A GUIDE TO MOLECULAR AND FUNCTIONAL INVESTIGATIONS OF PLATELETS TO BRIDGE BASIC AND CLINICAL SCIENCES Article 03 March 2022 PLATELET-PRIMED INTERACTIONS OF COAGULATION AND

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complex interplay between inhibitory and activatory networks. _J. Thromb. Haemost._ 14, 918–930 (2016). CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS The

authors thank the Cardiovascular Centre (HVC) of Maastricht University Medical Centre, The Netherlands, for support. We thank C. Baaten and J. van Geffen (Maastricht University, The

Netherlands) for their help in preparing the figures before submission. REVIEWER INFORMATION _Nature Reviews Cardiology_ thanks E. Gardiner, M. Gawaz, and the other, anonymous reviewer for

their contribution to the peer review of this work. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht

University, Maastricht, The Netherlands Paola E. J. van der Meijden & Johan W. M. Heemskerk Authors * Paola E. J. van der Meijden View author publications You can also search for this

author inPubMed Google Scholar * Johan W. M. Heemskerk View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Both authors researched data for the

article, discussed its content, wrote the manuscript, and reviewed and edited it before submission. CORRESPONDING AUTHORS Correspondence to Paola E. J. van der Meijden or Johan W. M.

Heemskerk. ETHICS DECLARATIONS COMPETING INTERESTS P.E.J.v.d.M. is a consultant at Bayer AG. J.W.M.H. is a founder and shareholder of FlowChamber BV. ADDITIONAL INFORMATION PUBLISHER’S NOTE

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. GLOSSARY * Fibrin coat Fibrin-coated platelets are a subpopulation of

phosphatidylserine-exposing platelets that bind fibrin via transglutaminase activity and activated integrin αIIbβ3. Fibrin is ‘coated’ on the platelet surface. * Membrane ballooning Adherent

platelets on a collagen surface form phosphatidylserine-exposing, balloon-like membrane structures as a result of salt and water entry into the platelets. * Procoagulant platelet Platelet

swollen to a balloon shape, with surface exposure of phosphatidylserine and displaying greatly increased capacity for coagulation factor activation. * Pseudopod formation Cytoplasm-filled

projection of the platelet membrane following platelet activation. * α-Granules Platelet secretion granules containing multiple stored proteins including growth factors. * δ-Granules

Platelet secretion granules with dense appearance in electron microscopy, containing Ca2+-bound nucleotides (ADP, ATP, and polyphosphates). * Plateletcrit Product of mean platelet volume and

platelet count in blood. * Negative or positive platelet priming Suppression or promotion of platelet activation by bioactive molecules in the blood. * Exhausted platelets Also known as

refractive platelets; platelets with reduced secretion capacity owing to previous activation. * Weibel–Palade bodies Storage granules of endothelial cells that store ultralarge von

Willebrand factor multimers. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE van der Meijden, P.E.J., Heemskerk, J.W.M. Platelet biology and functions:

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