Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans

摘要

OBJECTIVE—To determine whether there is evidence of platelet activation following in vivo cocaine administration in humans, as cocaine abuse is associated with myocardial infarction and stroke, and platelet activation leading to thrombosis is a possible mechanism.
SETTING—University hospital.
DESIGN AND SUBJECTS—Following a randomised, double blind crossover design, 14 healthy volunteers were studied twice, receiving cocaine (2 mg/kg intranasally) once and placebo once. Flow cytometric analysis of P-selectin expression (an α granule membrane protein found on the surface of activated platelets), quantification of the platelet specific proteins platelet factor 4 and β thromboglobulin, and measurement of platelet containing microaggregate and platelet microparticle (fragment) formation were used to assess platelet activation. Circulating von Willebrand factor antigen (vWF) was measured to evaluate a possible role of endothelial stimulation concurrent with platelet activation.
RESULTS—There was an increase in both platelet factor 4 (mean (SD), 16 (7) to 39 (22) IU/ml, p = 0.04) and β thromboglobulin (70 (20) to 98 (26) IU/ml, p < 0.01) at 120 minutes following cocaine administration. Platelet containing microaggregate formation was increased at 40 minutes (from 47 (3.2)% to 54 (2.0)%, p < 0.001) and 80 minutes (55 (2.5)%, p = 0.04). Bleeding time decreased following cocaine from 10 (1) to 9 (1) minutes (p = 0.07). No changes in any of the measured variables were noted following placebo administration.
CONCLUSIONS—Cocaine exposure causes platelet activation, α granule release, and platelet containing microaggregate formation. These data support the view that cocaine, even at the relatively low doses commonly self administered by occasional abusers, may promote thrombosis and predispose healthy individuals to ischaemic events. Platelet inhibitors should be considered early in any patient with suspected cocaine related ischaemia.


>Keywords: platelets; cocaine; flow cytometry; myocardial infarction