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 StudiesSubject(s)
Protease Inhibitors/classification , Thrombosis/physiopathology , alpha 1-Antichymotrypsin/physiology , alpha 1-Antitrypsin/drug effects , alpha 1-Antitrypsin/physiology , alpha-2-Antiplasmin/physiology , Antithrombin III/drug effects , Antithrombin III/physiology , Antithrombins/physiology , Blood Coagulation , Heparin/pharmacology , Peptide Hydrolases , Thrombin/metabolismABSTRACT
La alfa-manosiadasa (alfa m) es una hidrolasa ácida que se encuentra en los gránulos azurófilos de los leucocitos polimorfonucleares y en menor concentración en los linfocitos. En leucemias agudas no linfoides sus niveles se hallan muy aumentados respecto de los controles normales (p < 0,001). En estos pacientes, se encuentran alteraciones funcionales e inmunológicas de algunas glicoproteínas del sistema plasmático de coagulación y de fibrinólisis, tales como la antitrombina III (AT III), el fibrinógeno o factor I de coagulación (I) y el plasminógeno (Plg). Debido a esto, investigamos la acción de alfa m sobre estas proteínas purificadas, a partir de plasma humano normal, utilizando métodos inmunoelectroforéticos y electroforesis en gel de poliacrilamida con SDS. Se hallan modificaciones importantes en AT III y I y menores en Plg, similares a las obtenidas en los plasmas de los pacientes. Luego, parece que la acción de hidrolasas ácidas es posible in vivo bajo ciertas condiciones patológicas