title: The causal role of megakaryocyte–platelet hyperactivity in acute coronary syndromes.
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.
authors.affiliation: Center for Cardiovascular Biology and Medicine, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK. j.martin@ucl.ac.uk
authors.forename: John F
authors.initials: JF
authors.lastname: Martin
authors.forename: Steen D
authors.initials: SD
authors.lastname: Kristensen
authors.forename: Anthony
authors.initials: A
authors.lastname: Mathur
authors.forename: Erik L
authors.initials: EL
authors.lastname: Grove
authors.forename: Fizzah A
authors.initials: FA
authors.lastname: Choudry
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D001792:Blood Platelets / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D006487:Hemostasis; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology*; D034061:Thrombopoiesis