Abstract
Platelets are causally involved in coronary artery obstruction in acute coronary syndromes (ACS). This cell type is unique to mammals and its production, which is unlike that of any other mammalian cell, involves polyploid nuclear change in the mother cell (megakaryocyte) and the production of anucleate cells with a log Gaussian distribution of volume. Platelets vary more in cellular volume than any other circulating blood element in mammals. Larger platelets are denser, contain more secretory granules, and are more reactive than their smaller counterparts. A causal relationship between the presence of large, dense, reactive platelets in the circulation and ACS is supported by many clinical studies. Furthermore, the results of two large, prospective, epidemiological studies have demonstrated that mean platelet volume was the strongest independent predictor of outcome in patients with acute myocardial infarction. Notably, evidence indicates that an increase in mean platelet volume in the pathogenesis of ACS can potentially overwhelm current therapeutics. The control system for the physiological and pathophysiological production of large platelets should, therefore, be researched. An understanding of this system might give rise to new therapeutics that could control platelet reactivity and thereby comprehensively prevent ACS.
Key Points
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The megakaryocyte–platelet hemostatic system is unique to mammals, and has a complex control system that is not yet fully understood
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Larger platelets are denser and more reactive than smaller platelets, and are associated with megakaryocyte change
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Large clinical studies have shown a relationship between large platelets and incidence of acute coronary syndromes
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Two large prospective epidemiological studies have shown that the presence of large platelets can independently predict outcome related to acute myocardial infarction, including death
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Platelet physiological change has the potential to overwhelm current therapeutic interventions
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Future research should address the physiological and pathological production of large platelets
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Acknowledgements
J. F. Martin is an Adjunct Professor of Medicine at Yale University, New Haven, CT, USA. The authors would like to acknowledge Mattia Frontini, University of Cambridge, for his suggestions on megakaryocyte biology in revision of the manuscript.
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J. F. Martin and F. A. Choudry wrote the article. J. F. Martin, S. D. Kristensen, E. L. Grove, and F. A. Choudry had a substantial contribution to the discussion of content. J. F. Martin, S. D. Kristensen, E. L. Grove, and F. A. Choudry researched data for the article, and all authors reviewed and edited the manuscript before submission.
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Martin, J., Kristensen, S., Mathur, A. et al. The causal role of megakaryocyte–platelet hyperactivity in acute coronary syndromes. Nat Rev Cardiol 9, 658–670 (2012). https://doi.org/10.1038/nrcardio.2012.131
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DOI: https://doi.org/10.1038/nrcardio.2012.131
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