Platelet alpha-granule release in cocaine users.

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.

[1]  B. Smith,et al.  Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release , 1993 .

[2]  B. Smith,et al.  Activation in stored platelet concentrates: correlation between membrane expression of P‐selectin, glycoprotein IIb/IIIa, and beta‐ thromboglobulin release , 1993, Transfusion.

[3]  R. Hillman,et al.  The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis. , 1992, American journal of clinical pathology.

[4]  D. Silverman,et al.  Intravenous cocaine challenges during desipramine maintenance. , 1992, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[5]  C. Benjamin,et al.  Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets , 1992, Nature.

[6]  D. Triulzi,et al.  Detection and significance of alpha granule membrane protein 140 expression on platelets collected by apheresis , 1992, Transfusion.

[7]  G. Vetrovec,et al.  Frequency of coronary artery disease and left ventricle dysfunction in cocaine users. , 1992, The American journal of cardiology.

[8]  J. Mathew,et al.  Cardiopulmonary bypass induces leukocyte-platelet adhesion. , 1992, Blood.

[9]  M. Winniford,et al.  Cocaine-induced myocardial infarction in patients with normal coronary arteries. , 1991, Annals of internal medicine.

[10]  B. Smith,et al.  Dynamics of leukocyte-platelet adhesion in whole blood , 1991 .

[11]  J. Mathew,et al.  Modulation of platelet surface adhesion receptors during cardiopulmonary bypass. , 1991, Anesthesiology.

[12]  B. Smith,et al.  Activated and unactivated platelet adhesion to monocytes and neutrophils. , 1991, Blood.

[13]  R. Hillman,et al.  Platelet activation and aggregation during cardiopulmonary bypass. , 1991, Anesthesiology.

[14]  R. Virmani,et al.  Increase in atherosclerosis and adventitial mast cells in cocaine abusers: an alternative mechanism of cocaine-associated coronary vasospasm and thrombosis. , 1991, Journal of the American College of Cardiology.

[15]  R. Hillman,et al.  Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion , 1991, Transfusion.

[16]  D. Noe,et al.  A pharmacokinetic–pharmacodynamic model of heart rate during cocaine administration in humans , 1991, Clinical pharmacology and therapeutics.

[17]  N. Rote,et al.  Production of monoclonal antibodies specific for platelet activation antigens and their use in evaluating platelet function. , 1990, Hybridoma.

[18]  A. Marcus,et al.  Stratton lecture 1989. Thrombosis and inflammation as multicellular processes: pathophysiologic significance of transcellular metabolism. , 1990, Blood.

[19]  P. Jatlow,et al.  Determination of cocaine concentrations in plasma by high-performance liquid chromatography. , 1990, Clinical chemistry.

[20]  L. Hillis,et al.  Effect of cocaine on coronary artery dimensions in atherosclerotic coronary artery disease: enhanced vasoconstriction at sites of significant stenoses. , 1990, Journal of the American College of Cardiology.

[21]  W. Roberts,et al.  Quantitative analysis of amounts of coronary arterial narrowing in cocaine addicts. , 1990, The American journal of cardiology.

[22]  N. Mekhail,et al.  Cocaine-induced small vessel spasm in isolated rat hearts. , 1989, The American journal of pathology.

[23]  C. Lambrew,et al.  Correlated measurement of platelet release and aggregation in whole blood. , 1989, Cytometry.

[24]  R. Cook,et al.  Cloning of GMP-140, a granule membrane protein of platelets and endothelium: Sequence similarity to proteins involved in cell adhesion and inflammation , 1989, Cell.

[25]  S. Willich,et al.  Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. , 1987, The New England journal of medicine.

[26]  J. George,et al.  Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery. , 1986, The Journal of clinical investigation.

[27]  Simpson Rw,et al.  Pathogenesis of cocaine-induced ischemic heart disease. Autopsy findings in a 21-year-old man. , 1986 .

[28]  R. Ross.  The pathogenesis of atherosclerosis--an update. , 1986, The New England journal of medicine.

[29]  P. Jatlow,et al.  Plasma cocaine concentrations during cocaine paste smoking. , 1982, Life sciences.

[30]  C. Wetli,et al.  Death caused by recreational cocaine use. , 1979, JAMA.

[31]  R. Ross,et al.  The platelet-derived growth factor , 1978, Cell.

[32]  P. Jatlow,et al.  Cocaine: plasma concentrations after intranasal application in man , 1976 .

[33]  R. Ross,et al.  A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[34]  R. Roth,et al.  Cocaethylene: a neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion. , 1991, Life sciences.

[35]  C. Wetli,et al.  Cocaine and sudden "natural" death. , 1987, Journal of forensic sciences.

[36]  L. Caprino,et al.  Platelet responsiveness and biosynthesis of thromboxane and prostacyclin in response to in vitro cocaine treatment. , 1985, Haemostasis.