Platelet activation in chronic cocaine users: Effect of short term abstinence

Abstract

Cocaine abuse increases the risk of cardiac and cerebrovascular events, such as myocardial infarction and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation has been observed. The aim of this study was to investigate the existence of platelet activation and the effect of short-term abstinence in chronic cocaine consumers. We studied 23 cocaine dependent individuals (aged 20-54 years) who met DSM-IV criteria for cocaine dependence and 20 controls. Samples were obtained at baseline, within 72 h of last drug exposure and after 4 weeks of controlled abstinence. Monocyte-platelet aggregates (MPA) were measured by flow cytometry. Plasma levels of soluble CD40L (sCD40L), Neutrophil-Activating Peptide-2 (NAP-2) and regulated on activation normal T cells expressed and secreted (RANTES) were determined by ELISA. Levels of MPA, sCD40L, NAP-2 and RANTES were significantly higher (all p < 0.05) in cocaine addicts compared to controls at baseline. All the parameters returned to values similar to the control group after 4-weeks' abstinence. Levels of sCD40L and RANTES were associated with an index of intensity of drug consumption (p< 0.02). Our results demonstrate that cocaine use induces platelet activation which is a prominent finding after recent consumption. The persistence over time of this condition may contribute not only to acute thrombotic complications but also to the development of early-onset atherosclerotic process observed in cocaine abusers.

Atorvastatin Reduces the Proadhesive and Prothrombotic Endothelial Cell Phenotype Induced by Cocaine and Plasma From Cocaine Consumers In Vitro

“…The effect of plasma was exclusive of PFP-CP because PFP from noncocaine consumers did not induce either VWF release or platelet adherence. Our previous report showed that chronic cocaine users have elevated levels of several platelet 14 and EC 8 activation markers that remain in circulation beyond the half-life of cocaine metabolites. On the basis of the latter observation, our results on PFP stimulation and atorvastatin inhibition are of particular interest because these conditions may replicate the environment to which vascular endothelia of the addicted patients is exposed.…”

“…12,13 Platelet activation has also been implicated as a possible mechanism by which cocaine promotes thrombus formation. 14,15 Chronic cocaine consumption is associated with elevations of CD40L, neutrophil-activating protein-2 (CXCL7), and Regulated on Activation, Normal T Cell Expressed and Secreted levels in the plasma. The continuous presence of cocaine in circulation (as seen in chronic cocaine abusers) would provide an environment of constant stimulation for platelets, supporting their contribution to the development of ischemic-vascular complications associated with cocaine consumption.…”

Daño vascular asociado a uso de cocaína: Caso clínico

“…En este mismo sentido y en relación con las complicaciones trombóticas de la adicción, se ha demostrado activación de las plaquetas tanto en relación a uso agudo como crónico de cocaína 14,15 . En dependientes de cocaína observamos que después de consumo reciente existe activación de las plaquetas circulantes, demostrada por marcadores celulares y solubles, que regresan después de un mes de abstinencia 16 .…”

Infarto agudo al miocardio asociado al uso de cocaína: ¿una entidad diferente?

“…Estos incluyen activación simpaticomimética, vasoespasmo coronario, disfunción endotelial, trombosis y ateroesclerosis acelerada. La activación simpaticomimética propia de la cocaína conlleva un efecto inotrópico y cronotrópico positivo, aumentando además la presión arterial, todo lo cual conlleva a un aumento del stress de la pared del ventrículo izquierdo y a un mayor consumo de oxígeno; este mecanismo por sí sólo es incapaz de explicar la presencia de un infarto con elevación del ST. El vasoespasmo se ha descrito como consecuencia del consumo de cocaína 8 , pero reportes clínicos de pacientes con IAMC no han podido demostrar este efecto 3 . Los pacientes consumidores poseen marcadores de actividad plaquetaria aumentada 9 .…”

“…Todo lo anterior predispone a arterioesclerosis acelerada y un estado protrombótico. Desde el punto de vista angiográfico, los IAMC tienen mayor reporte de arterias coronarias sin lesiones significativas que van desde un 25 a un 40%, menos lesiones de 3 vasos 4 , y más incidencia de trombos [3][4][5][6][7][8][9][10][11][12][13][14] . Existiría una enfermedad ateroesclerótica más difusa con más cantidad de placas, pero estenosis menos severas 15 .…”