ABSTRACT
Background: Atrial fibrillation (AF) generates a hypercoagulable state with an increased thrombin generation and raised levels of thrombin-antithrombin complexes, which results in a high risk of stroke and thromboembolism. Aim: To evaluate the anticoagulant effect of rivaroxaban by anti-Xa factor activity and its correlation with thrombin-antithrombin complexes, thrombin generation and prothrombin time in patients newly diagnosed with non-valvular AF. Patients and Methods: Prospective study in patients with indication of anticoagulation. Demographic variables, cardiovascular risk factors, CHA2DS2-VASc and HAS-BLED scores were recorded. Blood samples were taken at baseline, at 3 and 24 hours after the administration of the drug and at 30 days. Rivaroxaban levels, anti-Xa activity, prothrombin time, thrombin generation and plasma levels of thrombin-antithrombin complexes were determined. Results: We studied 20 patients aged 76.3 ± 8.0 years (60% female) with a CHA2DS2-VASc score > 2 points. The anti-Xa factor activity correlated with rivaroxaban plasma levels at 3 hours (r = 0.61, p < 0.01), at 24 hours (r = 0.85, p < 0.01) and at 30 days (r = 0.99, p < 0.01), with prothrombin time at 3 hours (r = -0.86, p = 0.019) and at 30 days (r = -0.63, p = 0.02) and with a sustained decrease in thrombin generation at 30 days of follow-up (r = -0.74, p < 0.01). There was no correlation with thrombin-antithrombin complexes (r = -0.02, p = 0.83). Conclusions: Rivaroxaban consistently inhibited the mild pro-coagulant state found in newly diagnosed non-valvular AF patients through the first 24 hours and this effect was maintained at 30 days. Plasma levels of the drug correlated with anti-Xa factor activity, thrombin generation and prothrombin time
Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Peptide Hydrolases/drug effects , Atrial Fibrillation/blood , Thrombin/drug effects , Factor Xa/drug effects , Antithrombin III/drug effects , Factor Xa Inhibitors/pharmacology , Rivaroxaban/pharmacology , Prothrombin Time , Time Factors , Thrombin/metabolism , Factor Xa/metabolism , Administration, Oral , Prospective StudiesABSTRACT
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...
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...
Subject(s)
Humans , Male , Adult , Female , Middle Aged , Cocaine/pharmacology , Endothelium, Vascular , Endothelium, Vascular/physiopathology , Hemostasis , Cocaine-Related Disorders/complications , Chronic Disease , Cocaine/adverse effectsABSTRACT
Introducción: Las estatinas han demostrado disminuir los eventos cardiovasculares en sujetos con y sin enfermedad aterosclerótica establecida. Se ha demostrado, que sus efectos benéficos no sólo dependen de la reducción del colesterol, sino que también podrían ser secundarios a otros efectos de las estatinas, como su efectos de reducción de inflamación y/ o trombogénesis entre otros. Sin embargo, no existen trabajos que demuestren que las estatinas sean capaces de frenarla activación de la cascada de inflamación y/o trombogénesis. Objetivos: Determinar el efecto de la administración oral de atorvastatina por 7 días sobre los niveles plasmáticos de proteína C- reactiva ultrasensible (PCR us), fibrinógeno y P-selectina, pre y post prueba de esfuerzo máximo inmediato y a las 24 horas de su ejecución. Métodos: Ensayo clínico en 50 hombres sanos (18 a 50 años), randomizado atorvastatina 80 mg/día - placebo por 7 días, doble ciego. Muestras tomadas en sangre para PCRus, fibrinógeno y P-selectina, perfil lipídico, creatin kinasa y transaminasas hepáticas, pre y post test de esfuerzo, y a las 24 horas. Los resultados para datos continuos se expresan como medias +/- desviación estándar, test de student para muestras independientes, ANOVA para muestras repetidas. Programa estadístico SPSS 14.0. Resultados: Un grupo de 44 sujetos completaron el estudio: atorvastatina 80 mg (n=24) o placebo (n=20). En el grupo atorvastatina, después de una semana de tratamiento, los niveles de LDLc disminuyeron en 38 por ciento (LDL basal: 97 +/- 27 mg/dL vs LDL post: 62 +/- 31 mg/dL, p < 0.001). Sin embargo, no se observaron cambios en ese mismo período en los niveles de PCRus, fibrinógeno y P-selectina con respecto a placebo. Los niveles de fibrinógeno se elevaron 8 por ciento entre la etapa pre y post ejercicio inmediato (341 +/- 56 mg/dL vs 368 +/- 65 mg/dL, p<0.001), retornando a los niveles basales a las 24 horas; no hubo diferencias entre atorvastatina - placebo...
Background: Chronic statin therapy is known to decrease ínflammation and platelet aggregation. However, little data exist regarding acute effect of statins upon these variables. Exercise can be used to induce ínflammation and platelet aggregation. Aim: to determine the acute effect of atorvastatin upon plasma levels of ultra sensitive C reactive protein (US-PCR), fibrinogen and P selectin before, immediately after and 24 hr following a maximal exercise test in healthy subjects. Methods: This was a double blind, randomized prospective study Fifty healthy male subjects (aged 18to 50years) received atorvastatin 80 mg or placebo daily for 7 days. US-PCR, fibrinogen, P-selectin, blood lipids, total creatin-kinase (CK) and transaminases were determined pre and immediately after maximal treadmill exercise. Repeat determinations were performed 24 following the test. Results were analyzed using the SPSS statistical package, and are expressed as mean +/- SD. Student's t and repeated measures ANOVA were used as appropriate. Results: 44 subjects completed the study (atorvastatin =24; placebo= 20). LDL cholesterol decreased from 97 +/- 27 to 62 +/- 31 mg/dl in the atorvastatin group (p<0.001). US-PCR, After 1 week, Fibrinogen and P-selectin were not significantly modified from baseline, and no differences were observed between groups (atorvastatin vs. control). However, fibrinogen increased 8 percent from baseline to immediately post exercise (341 +/- 6 vs. 368 +/- 65mg/dl (95 percent CI. 21/.3 - 33.6). 24hr after exercise, fibrinogen levels returned to baseline. Similar changes were observed for P-selectin (25 +/- 5, 28 +/- 1.7 ng/dl, baseline and post exercise respectively p<0.01), again returning to baseline 24hr after exercise. No significant changes were observed for US-PCR after exercise in neither group. CK increased 43 percent in the atorvastatin group and 12 percent in controls (NS). Conclusion: Atorvastatin...