Measurement of coagulation factors during rivaroxaban and apixaban treatment: Results from two crossover trials.

Background: Prediction models for venous thromboembolism recurrence will likely be improved by adding levels of coagulation factors. Risk assessment is ideally performed during anticoagulant treatment, however, the influence of direct oral anticoagulants on coagulation factors is uncertain.

Objective: To assess the influence of rivaroxaban and apixaban on several coagulation factor levels.

Methods: In two crossover trials we assessed the influence of rivaroxaban and apixaban intake on factor (F)VIII, FXI and FXII-activity and fibrinogen, von Willebrand factor (VWF:Ag), and d-dimer levels. At three sessions with a washout period in between, blood was taken from 12 healthy male individuals immediately before intake of rivaroxaban 15 mg twice daily (n = 6) or apixaban 10 mg twice daily (n = 6) and three hours after the last intake.

Results: Overall, measured levels were lower after rivaroxaban/apixaban intake. The paired mean difference after rivaroxaban intake was -38 IU/dL (95% CI -43; -33) for FVIII:C, -29 U/dL (95% CI -45; -12) for FXI:C, -22 IU/dL (95% CI -43; -1) for FXII:C, -0.11 g/L (95% CI -0.25; 0.03) for fibrinogen, -7 IU/dL (95% CI -18; 3) for VWF:Ag, -27 ng/mL (95% CI -50; -4) for d-dimer and -0.36 (95% CI -0.57; -0.15) for Ln d-dimer. After apixaban intake this was -29 IU/dL (95% CI -38; -21) for FVIII:C, -29 IU/dL (95% CI -36; -22) for FXI:C, -19 IU/dL (95% CI -24; -15) for FXII:C, -0.18 g/L (95% CI -0.33; 0.03) for fibrinogen, -52 ng/mL (95% CI -100; -4) for d-dimer, 0.25 (-0.60; 0.09) for Ln d-dimer and 1 IU/dL (95% CI -7; 9) for VWF:Ag.

Conclusion: FVIII:C, FXI:C, FXII:C, and d-dimer measurements were influenced by rivaroxaban/apixaban intake, while fibrinogen and VWF:Ag were not.