Heterogeneity of platelets and their responses

There has been increasing recognition of heterogeneity in blood platelets and their responses, particularly in recent years, where next-generation technologies and advanced bioinformatic tools that interrogate "big data" have enabled large-scale studies of RNA and protein expression across a growing list of disease states. However, pioneering platelet biologists and clinicians were already hypothesizing upon and investigating heterogeneity in platelet (and megakaryocyte) activity and platelet metabolism and aggregation over half a century ago. Building on their foundational hypotheses, in particular Professor Marian A. Packham's pioneering work and a State of the Art lecture in her memoriam at the 2023 International Society on Thrombosis and Haemostasis Congress by Anandi Krishnan, this review outlines the key features that contribute to the heterogeneity of platelets between and within individuals. Starting with important epidemiologic factors, we move stepwise through successively smaller scales down to heterogeneity revealed by single-cell technologies in health and disease. We hope that this overview will urge future scientific and clinical studies to recognize and account for heterogeneity of platelets and aim to apply methods that capture that heterogeneity. Finally, we summarize other exciting new data presented on this topic at the 2023 International Society on Thrombosis and Haemostasis Congress.