Sarah Bos

50 CHAPTER 4 Abstract Background: patients with cirrhosis are at risk for bleeding and thrombosis. In management of thromboses, direct oral anticoagulants (DOAC) have clear advantages over traditional anticoagulants, since they are orally administered without the need for monitoring. The safety and efficacy of DOACs in cirrhosis has not been extensively studied, and the optimal dose in these patients is unknown. Methods: we administered a therapeutic dose of edoxaban (60 mg, once daily) for one week to 16 patients with cirrhosis (15 with Child A, and 1 with Child B cirrhosis) and 16 healthy controls, and drew blood at various time points. We studied calibrated automated thrombinography, edoxaban-calibrated anti-Xa levels, and D-dimer levels at baseline, and at peak level on day 1, 3 and 7. Results: at baseline, the median endogenous thrombin potential (ETP) of patients was higher compared to healthy subjects. On day 1, 3, and 7, the ETP in both patients and healthy subjects was substantially lower compared to baseline, but remained significantly higher in patients. In addition, D-dimer levels decreased over time in controls, but not in patients. Edoxaban plasma levels were similar in patients and controls. Conclusion: therapeutic dose of the DOAC edoxaban strongly decreases ETP in patients with cirrhosis and in controls, but hemostatic activity remains higher in patients. Whether this difference translates into a higher risk of thrombosis and necessitates dose-adjustments in patients with cirrhosis should be further assessed.