This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rinder, H. M. Articles by Smith, B. R. Search for Related Content PubMed PubMed Citation Articles by Rinder, H. M. Articles by Smith, B. R.

Circulation, Vol 90, 1162-1167, Copyright © 1994 by American Heart Association

ARTICLES

Platelet alpha-granule release in cocaine users

HM Rinder, KA Ault, PI Jatlow, TR Kosten and BR Smith
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Conn. 06520-8035.

BACKGROUND: Cocaine use has been associated with arterial occlusion resulting from platelet-rich thrombi and with an accelerated, often atypical atherosclerotic lesion that could be ascribed to platelet activation and platelet alpha-granule release. METHODS AND RESULTS: Using a flow cytometric method to quantitate the percent of circulating activated platelets in whole blood (those that express the alpha- granule membrane protein P-selectin), we found that 5 of 25 samples from 12 long-term cocaine users had a baseline level of circulating activated platelets > 3 SD (range, 19% to 60%) above the mean (4.4 +/- 3.7%, mean +/- 1 SD) for 85 nonusers (sample n = 130). This subset resulted in a significantly higher mean baseline level of circulating activated platelets (11.8 +/- 14.4%) for all cocaine users (P = .01). By contrast, cocaine and its metabolites, at concentrations documented as obtainable during in vivo cocaine use (10(-7) to 10(-5) mol/L), had no effect on in vitro platelet activation or aggregation, either directly or in concert with platelet agonists. However, in experiments in which cocaine users received blinded infusions of placebo or cocaine, the mean percent of circulating activated platelets rose significantly (P < .05) after infusion of either placebo (peak 77 +/- 31%) or cocaine (peak 65 +/- 28%), the latter at doses resulting in peak plasma cocaine levels averaging < 10(-6) mol/L. CONCLUSIONS: Long- term cocaine use in some subjects is intermittently associated with high basal levels of circulating platelets that have undergone alpha- granule release. The inability of cocaine and its metabolites at concentrations of 10(-7) to 10(-5) mol/L to cause platelet P-selectin expression in vitro in this study, coupled with the acute increase in circulating activated platelets observed in vivo after either cocaine or placebo infusion, suggests that in vivo platelet alpha-granule release associated with cocaine use may occur through indirect rather than direct effects of the drug.

This article has been cited by other articles:

				J. McCord, H. Jneid, J. E. Hollander, J. A. de Lemos, B. Cercek, P. Hsue, W. B. Gibler, E. M. Ohman, B. Drew, G. Philippides, et al. Management of Cocaine-Associated Chest Pain and Myocardial Infarction: A Scientific Statement From the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology Circulation, April 8, 2008; 117(14): 1897 - 1907. [Full Text] [PDF]

				S. D Treadwell and T. G Robinson Cocaine use and stroke Postgrad. Med. J., June 1, 2007; 83(980): 389 - 394. [Abstract] [Full Text] [PDF]

				S L Greene, P I Dargan, and A L Jones Acute poisoning: understanding 90% of cases in a nutshell Postgrad. Med. J., April 1, 2005; 81(954): 204 - 216. [Abstract] [Full Text] [PDF]

				R. A. Lange and L. D. Hillis Cardiovascular Complications of Cocaine Use N. Engl. J. Med., August 2, 2001; 345(5): 351 - 358. [Full Text] [PDF]

				C M Heesch, C R Wilhelm, J Ristich, J Adnane, F A Bontempo, and W R Wagner Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans Heart, June 1, 2000; 83(6): 688 - 695. [Abstract] [Full Text]

				A. J. Siegel, M. B. Sholar, J. H. Mendelson, S. E. Lukas, M. J. Kaufman, P. F. Renshaw, J. C. McDonald, K. B. Lewandrowski, F. S. Apple, J. J. Stec, et al. Cocaine-Induced Erythrocytosis and Increase in von Willebrand Factor: Evidence for Drug-Related Blood Doping and Prothrombotic Effects Arch Intern Med, September 13, 1999; 159(16): 1925 - 1929. [Abstract] [Full Text] [PDF]

				M J A Williams, N J Restieaux, and C J S Low Myocardial infarction in young people with normal coronary arteries Heart, February 1, 1998; 79(2): 191 - 194. [Abstract] [Full Text]

				J. E. Hollander, D. E. Brooks, and S. M. Valentine Assessment of Cocaine Use in Patients With Chest Pain Syndromes Arch Intern Med, January 12, 1998; 158(1): 62 - 66. [Abstract] [Full Text] [PDF]