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Abstract
Although lacking a nucleus, platelets are increasingly recognized not only for their complexity, but also for their diversity. Some 50 years ago platelet subpopulations were characterized by size and density, and these characteristics were thought to reflect platelet aging. Since, our knowledge of platelet heterogeneity has grown to recognize that differences in platelet biochemistry and function exist. This includes the identification of vanguard and follower platelets, platelets with differing procoagulant ability including “COAT-platelets” which enhance procoagulant protein retention on their surface, and most recently, the identification of platelet subpopulations with a differential ability to generate and respond to nitric oxide. Hence, in this mini-review, we summarize the current knowledge of platelet subpopulation diversity focusing on their physical, biochemical, and functional heterogeneity. In addition, we review how platelet subpopulations may change between health and disease and how differences among platelets may influence response to anti-platelet therapy. Finally, we look forward and discuss some of the future directions and challenges for this growing field of platelet research.
Highlights
Compared to leukocytes, which exist as functionally distinct subpopulations, platelets have often been considered simple
Large-dense platelets would be expected to arise from 8n megakaryocytes with greater granule content, while small-light platelets arise from 32n megakaryocytes. This view was more in line with that of Paulus that thrombopoiesis is likely responsible for platelet heterogeneity and not aging in circulation, but that only a single platelet population exists and the only size heterogeneity is that inherent to the log normally distributed population [25]
Similar to the findings of Opper et al [42], which suggested differences in NO-signaling between low and high density platelet subpopulations, recently we identified human platelet subpopulations based on the presence or absence of endothelial nitric oxide synthase and the differential ability to produce NO [47]
Summary
Our knowledge of platelet heterogeneity has grown to recognize that differences in platelet biochemistry and function exist This includes the identification of vanguard and follower platelets, platelets with differing procoagulant ability including “COAT-platelets” which enhance procoagulant protein retention on their surface, and most recently, the identification of platelet subpopulations with a differential ability to generate and respond to nitric oxide. In this mini-review, we summarize the current knowledge of platelet subpopulation diversity focusing on their physical, biochemical, and functional heterogeneity.
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