Sarah Bos

59 Anticoagulant activity of edoxaban in patients with cirrhosis 4 In published studies, Xa-directed DOACs dosing tends to be conservative with reduced or low doses in a large proportion of patients.(8,11,19,20) Also in the ongoing Cirroxaban trial (clinicaltrials.gov NCT02643212), which is a placebo- controlled trial on Rivaroxaban in cirrhosis, a reduced dose was chosen. We have only studied patients with mild cirrhosis, and future studies should explore pharmacokinetics and -dynamics of DOACs in patients with more advanced disease that are at increased risk for both thrombotic and bleeding complications. Nevertheless, given the hypercoagulable state of patients with cirrhosis of all severities,(21) our results argue for a reevaluation of the conservative dosing regimens that have been used so far. However, although more stringent anticoagulation might lead to a better efficacy, it might also increase bleeding risk in these patients with a known complex and vulnerable hemostatic status.(1,2) Taken together, edoxaban plasma levels are similar between patients with cirrhosis and healthy controls after 7 days of treatment. However, edoxaban less efficiently reduces ex vivo hemostatic potential and in vivo activation of coagulation. These data suggest that reduced dosing is not necessary and would lead to undertreatment which is not desirable in these already hypercoagulable patients. Whether dose escalations are warranted requires further study.