Activation of human platelets by cocaine.
BACKGROUND
Cocaine ingestion has been associated with thrombosis of coronary as well as peripheral arteries, but the mechanism by which cocaine promotes thrombus formation is unknown. Accordingly, we determined whether cocaine activates human platelets by flow cytometric analysis of whole blood to which cocaine was added.


RESULTS
Activated platelets were detected by "two-color" flow cytometric analysis of the binding of fluorescently labeled antibodies directed against either platelet-associated fibrinogen or P-selectin, which are found on the surface of platelets only after stimulation. Platelets were distinguished from other constituents of whole blood by their ability to bind an anti-glycoprotein Ib antibody bound to both activated and resting platelets. Incubation of whole blood with cocaine, in concentrations of 10 microM to 13 mM, induced significant increases in both platelet-associated fibrinogen (range of increase, 45 +/- 12% to 125 +/- 40%) and P-selectin expression (36 +/- 15% to 112 +/- 24%). In platelets suspended in either buffer or plasma, however, P-selectin expression was detected only at the highest cocaine concentration (85 +/- 13% increase in plasma and 59 +/- 7% in buffer). Neither aspirin nor the ADP scavenger apyrase inhibited cocaine-induced P-selectin expression. Cocaine inhibited the uptake of 14C-radiolabeled serotonin by platelets (IC50, 8.7 microM). P-selectin expression and fibrinogen binding were found after the addition of cocaine alone to blood taken from some but not all donors; however, platelet activation in response to submaximal concentrations of the agonists ADP or epinephrine was enhanced by a low concentration of cocaine added to blood from every donor.


CONCLUSIONS
Cocaine, in concentrations similar to those found clinically, induces activation of individual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocaine. Thus, cocaine-induced platelet activation may contribute to thrombosis following cocaine ingestion.
Kugelmass
A D
AD
Charles A. Dana Research Institute, Beth Israel Hospital, Boston, MA 02215.
Oda
A
A
Monahan
K
K
Cabral
C
C
Ware
J A
JA
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis; D003042:Cocaine / Q000494:pharmacology*; D005340:Fibrinogen / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D019007:P-Selectin; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D013927:Thrombosis / Q000139:chemically induced
D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen; D003042:Cocaine