Daño endotelial y activación del sistema hemostático asociado al uso crónico de cocaína: estudios ex vivo e in vitro / Endothelial damage and activation of the haemostatic system associated to chronic use of cocaine: an ex vivo and in vitro study

RESUMEN

Antecedentes: Usuarios crónicos de cocaína tienen riesgo aumentado de presentar infarto de miocardio, angina,muerte súbita y accidentes cerebrovasculares. Aunque la patogenia del daño vascular es mayormente desconocida, se ha encontrado arterioesclerosis prematura y formación de trombos intravasculares. Objetivo: Demostrar evidencia de daño endotelial y activación del sistema hemostático en usuarios crónicos de cocaína. Métodos: Un grupo de 23 pacientes con criterios de dependencia a cocaína DSM-IV; 19 hombres (edad promedio 32 a), con exposición a la droga dentro de 72 h del estudio. Disfunción endotelial se evaluó por enumeración de las células endoteliales circulantes (CEC) y nivel de sICAM . Para activación del sistema hemostático se incluyó: complejos trombina-antitrombina (TAT) y generación de trombina; NAP-2 y RANTES para activación plaquetaria. In vitro, CE en cultivo (HUVEC), se expusieron a plasma de consumidores o controles. Se midió factor von Willebrand (FVW) en el medio y expresión de FvW y factor tisular (FT) sobre las CE. Adhesión plaquetaria estática se evaluó por microscopía. Resultados: En usuarios de cocaína, con respecto a controles, las CEC estaban significativamente elevadas...

ABSTRACT

Background: chronic cocaine users have an increased risk of developing myocardial infarction, angina, suddendeath and stroke. Although the pathogenesis of this effect is not completely known, premature atheromatosis and intravascular thrombosis appear to be involved.Aim: to provide evidence for the presence of endothelial damage and activation of the haemostatic system in chronic cocaine users. Methods: 23 subjects (19males, overall mean age 32) with DSM-IV criteria for cocaine dependency and exposure to the drug within 72 hours were studied. Endothelial dysfunction was determined by circulating endothelial cell counts (CEC) and sICAM levels. Thrombin-antithrombin complexes (TAT) and thrombin generation were used to characterize haemostatic status. In vitro, platelet activation was studied by NAP-2 and RANTES. EC in culture (HUVEC) were exposed to plasma from cocaine users and controls. Von Willebrand factor was measured in the culture media as well as its expression along with that of tissue factor in EC. Platelet adhesion was evaluated by microscopy. Results: Compared to controls, EC were significantly increased in cocaine users...