Circulation. 2001;104:1533-1537
doi: 10.1161/hc3801.095588
doi: 10.1161/hc3801.095588
(Circulation. 2001;104:1533.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Circulating Monocyte-Platelet Aggregates Are a More Sensitive Marker of In Vivo Platelet Activation Than Platelet Surface P-Selectin
Studies in Baboons, Human Coronary Intervention, and Human Acute Myocardial Infarction
From the Center for Platelet Function Studies (A.D.M., M.R.B., L.A.K., M.I.F.) and Division of Cardiovascular Medicine (M.I.F.), Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester, and the Naval Blood Research Laboratory (C.R.V.), Boston University School of Medicine, Boston, Mass.
Correspondence to Alan D. Michelson, MD, Director, Center for Platelet Function Studies, University of Massachusetts Medical School, Room S5-846, 55 Lake Ave N, Worcester, MA 01655. E-mail michelson{at}platelets.org
Background— Platelet surface P-selectin is considered the "gold standard" marker of platelet activation. Degranulated, P-selectin–positive platelets, however, aggregate with leukocytes in vitro and rapidly lose surface P-selectin in vivo.
Methods and Results— Flow cytometric tracking of autologous, biotinylated platelets in baboons enabled us to directly demonstrate for the first time in vivo that (1) infused degranulated platelets very rapidly form circulating aggregates with monocytes and neutrophils, and (2) 30 minutes after infusion of the degranulated platelets, the percentage of circulating monocytes aggregated with infused platelets persist at high levels, whereas the percentage of circulating neutrophils aggregated with infused platelets and the platelet surface P-selectin of nonaggregated infused platelets return to baseline. We therefore performed 2 clinical studies in patients with acute coronary syndromes. First, after percutaneous coronary intervention (n=10), there was an increased number of circulating monocyte-platelet (and to a lesser extent, neutrophil-platelet) aggregates but not P-selectin–positive platelets. Second, of 93 patients presenting to an Emergency Department with chest pain, patients with acute myocardial infarction (AMI) (n=9) had more circulating monocyte-platelet aggregates (34.2±10.3% [mean±SEM]) than patients with no AMI (n=84, 19.3±1.4%, P<0.05) and normal control subjects (n=10, 11.5±0.8%, P<0.001). Circulating P-selectin–positive platelets, however, were not increased in chest pain patients with or without AMI.
Conclusions— As demonstrated by 3 independent means (in vivo tracking of activated platelets in baboons, human coronary intervention, and human AMI), circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin.
Key Words: platelets • leukocytes • tests • coronary disease • receptors
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