PLATELET ALPHA-GRANULE RELEASE IN COCAINE USERS

Background Cocaine use has been associated with arterial occlusion res ulting from platelet-rich thrombi and with an accelerated, often atypi cal atherosclerotic lesion that could be ascribed to platelet activati on and platelet alpha-granule release. Methods and Results Using a flo w cytometric method to quantitate the percent of circulating activated platelets in whole blood (those that express the alpha-granule membra ne protein P-selectin), we found that 5 of 25 samples from 12 long-ter m cocaine users had a baseline level of circulating activated platelet s >3 SD (range, 19% to 60%) above the mean (4.4+/-3.7%, mean+/-1 SD) f or 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 me tabolites, at concentrations documented as obtainable during in vivo c ocaine use (10(-7) to 10(-5) mol/L), had no effect on in vitro platele t activation or aggregation, either directly or in concert with platel et agonists. However, in experiments in which cocaine users received b linded infusions of placebo or cocaine, the mean percent of circulatin g activated platelets rose significantly (P<.05) after infusion of eit her 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 u ndergone alpha-granule release. The inability of cocaine and its metab olites 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 in crease in circulating activated platelets observed in vivo after eithe r cocaine or placebo infusion, suggests that in vivo platelet cu-granu le release associated with cocaine use may occur through indirect rath er than direct effects of the drug.