Cocaine-induced platelet defects.
OBJECTIVE
Numerous studies have demonstrated an association between acute cardiac events, cerebrovascular accidents, and cocaine use. The underlying mechanisms leading to these complications have not been well defined. Using various in vitro model systems, it has been reported that cocaine, up to or greater than an order of magnitude of the lethal dose, causes either inhibitory or proaggregatory effects on platelet function.


METHODS
To address these reported discrepancies, we examined the effect of cocaine and its carrier on the activation and aggregation of human platelets in vitro.


RESULTS
We found that cocaine inhibited platelet aggregation when platelets were challenged with ADP, collagen, or arachidonic acid. This inhibition was due to a direct effect on fibrinogen binding to the activated platelet. Cocaine also caused the dissociation of preformed platelet aggregates. At these same concentrations, cocaine did not inhibit agonist-mediated increases in cytosolic calcium or inhibit platelet shape change, suggesting that its effect on platelet aggregation was a selective process and not due to a total destruction of platelet function. Interestingly, the organization of the cytoskeleton of activated platelets, a secondary event critical to cell receptor clustering and clot retraction, was disrupted by cocaine treatment. In addition, alterations in platelet protein electrophoretic patterns were observed on preincubation of platelets with cocaine.


CONCLUSIONS
We conclude that cocaine may have a direct inhibitory effect on the ability of platelets to participate in thrombus formation. The contribution of this effect as an underlying mechanism of sudden death in cocaine abusers is unknown.
Jennings
L K
LK
Department of Medicine, University of Tennessee, Memphis.
White
M M
MM
Sauer
C M
CM
Mauer
A M
AM
Robertson
J T
JT
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects* / Q000494:pharmacology; D003094:Collagen; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D003042:Cocaine; D002118:Calcium