Laboratory monitoring of novel oral anticoagulants rivaroxaban and dabigatran

Background: Rivaroxaban and dabigatran are new oral anticoagulants that both have been licensed worldwide for the treatment of atrial fibrillation and rivaroxaban also for venous thrombosis. Both drugs specifically inhibit one coagulation factor, factor Xa and thrombin, respectively, and both compounds have stable pharmacologic profiles, making regular monitoring as rewuired for Vitamin K antagonists unnecessary. However, in specific circumstances, such as in renal insufficiency, patients using these anticoagulant drugs may need laboratory monitoring and perhaps dose adjustments. Aims : The aim of this study was to assess a proper monitoring method for both drugs. Methods and Results: Samples were used from a cross-over study in healthy volunteers, originally designed to find a method of reversal for both anticoagulants (Eerenberg et al, Circulation, 2011). Twelve healthy male volunteers received rivaroxaban 20 mg twice daily, and dabigatran 150 mg twice daily for two and a half days, with a washout period of 11 days. Blood was drawn at the end of each treatment period. Following rivaroxaban treatment, the median plasma concentration was 273 μg/L, with an almost three fold difference in the interquartile range (158-393). Rivaroxaban significantly prolonged the anti-FXa assay and prothrombin time (PT), and both assays showed the best correlation with plasma concentrations (rho 0.63 for the anti- FXa assay and 0.47 for the PT). Dabigatran administration led to a median plasma concentration of 88 μg/L, with also a nearly three fold variability in the interquartile range (54-133). Dabigatran increased the activated partial thromboplastin time (aPTT), the Hemoclot and ecarin clotting time (ECT) significantly, and all assays correlated well with plasma concentrations (rho 0.99, 0.99 and 0.97, respectively). Conclusions: Plasma concentrations of rivaroxaban and dabigatran in healthy volunteers show considerable variability. Coagulation assays that corresponded well with plasma concentrations are the anti- FXa and PT for rivaroxaban, and the aPTT, Hemoclot and ECT for dabigatran