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. 2000 Jun;83(6):688–695. doi: 10.1136/heart.83.6.688

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

C Heesch 1, C Wilhelm 1, J Ristich 1, J Adnane 1, F Bontempo 1, W Wagner 1
PMCID: PMC1760877  PMID: 10814631

Abstract

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

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Figure 1  .

Figure 1  

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Representative flow cytometric tracing at (A) baseline and (B) 80 minutes after cocaine administration (bottom panel). The y axis measures fluorescence for the platelet marker CD42b, and the x axis measures forward light scatter, both in relative units. The field to the left (R1) represents the platelet fragment population. The middle field (R2) represents the population of single platelets, and platelet containing microaggregates are contained in field R3. There was a pronounced increase in microaggregates following cocaine administration.

Figure 2  .

Figure 2  

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Changes in heart rate (HR), systolic blood pressure (SPB), and diastolic blood pressure (DBP) preceding and following the administration of cocaine (black symbols) or placebo (white symbols). Values are means, error bars = SEM.

Figure 3  .

Figure 3  

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Changes in (A) platelet factor 4 and (B) β thromboglobulin at 120 minutes; both variables were significantly increased from baseline. Values are means, error bars = SEM.

Figure 4  .

Figure 4  

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Changes in (A) P-selectin expression (per cent of single platelet population also positive for CD62) and (B) microaggregate formation (expressed as per cent of all CD42b positive event). No changes were seen in P-selectin expression, whereas microaggregates were increased at 40 and 80 minutes. Values are means, error bars = SEM.

Figure 5  .

Figure 5  

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Results of bleeding time determinations for each individual at baseline and 120 minutes after the administration of cocaine.

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