ACTIVATION OF HUMAN PLATELETS BY COCAINE

Background. Cocaine ingestion has been associated with thrombosis of c oronary as well as peripheral arteries, but the mechanism by which coc aine promotes thrombus formation is unknown. Accordingly, we determine d whether cocaine activates human platelets by flow cytometric analysi s of whole blood to which cocaine was added. Methods and Results. Acti vated platelets were detected by two-color'' flow cytometric analysis of the binding of fluorescently labeled antibodies directed against ei ther platelet-associated fibrinogen or P-selectin, which are found on the surface of platelets only after stimulation. Platelets were distin guished from other constituents of whole blood by their ability to bin d an anti-glycoprotein Ib antibody bound to both activated and resting platelets. Incubation of whole blood with cocaine, in concentrations of 10 muM to 13 mM, induced significant increases in both platelet-ass ociated fibrinogen (range of increase, 45+/-12% to 125+/-40%) and P-se lectin expression (36+/-15% to 112+/-24%). In platelets suspended in e ither buffer or plasma, however, P-selectin expression was detected on ly at the highest cocaine concentration (85+/-13% increase in plasma a nd 59+/-7% in buffer). Neither aspirin nor the ADP scavenger apyrase i nhibited cocaine-induced P-selectin expression. Cocaine inhibited the uptake of C-14-radiolabeled serotonin by platelets (IC50, 8.7 muM). P- selectin expression and fibrinogen binding were found after the additi on of cocaine alone to blood taken from some but not all donors; howev er, platelet activation in response to submaximal concentrations of th e agonists ADP or epinephrine was enhanced by a low concentration of c ocaine added to blood from every donor. Conclusions. Cocaine, in conce ntrations similar to those found clinically, induces activation of ind ividual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocain e. Thus, cocaine-induced platelet activation may contribute to thrombo sis following cocaine ingestion.