Sarah Bos

124 CHAPTER 7 Based on plasma levels of edoxaban an optimal anticoagulant effect of edoxaban is reached in patients with cirrhosis with normal therapeutic dosages. However, the on-drug ETP and d-dimer levels might suggest that an even higher, supratherapeutic dosage is needed for adequate anticoagulant effect. When testing such escalated dose regiments, monitoring of drug levels with edoxaban calibrated anti-Xa assays might be a helpful tool to check and possible adjust dosages in patient with cirrhosis. Drug level monitoring is particularly relevant with prolonged use since cirrhosis is prone for deterioration over time and decreased hepatic and or renal clearance might occur.(25) However, it is unclear whether the ETP findings have clinical consequences, i.e., that a therapeutic dose of edoxaban is less effective to prevent thrombosis in patients with cirrhosis compared to other patients. It is far too early to advocate higher therapeutic doses before a better assessment of the efficacy in patients with cirrhosis and thrombosis has been performed. Furthermore, the value of anti-Xa assessment to target DOAC treatment is uncertain. Whether this is useful in patients with cirrhosis remains to be established. There are several retrospective clinical studies that used different DOACs in different dosages without a clear dosing rational. Many of these studies use reduced dosages for patients with cirrhosis.(8,11,16,17) Some of these studies compared DOACs with traditional anticoagulants. Although these studies did not show a difference in adverse events between the two regimens (DOACs and traditional anticoagulants), it is unclear whether DOACs were as effective as traditional anticoagulants.(33–38) Hanafy et al. were one of the first to publish on a full dose treatment of rivaroxaban for portal vein thrombosis in hepatitis C cirrhosis.(39) The treatment regimen consisted of rivaroxaban 10 mg twice daily. Compared to warfarin, thrombus resolution rates on ultrasound of the group receiving rivaroxaban were higher with less side effects. Before initiation of the treatment, both groups had similar MELD-scores. A significant decrease in MELD score was seen in the group treated with rivaroxaban compared to the warfarin group. These results are in line with the study of Villa in which a low dose of enoxaparin delayed the occurrence of decompensated cirrhosis and improved survival.(40) The results of this study are promising and hopefully lead to the expansion of our therapeutic options for the treatment of thrombosis in patients with cirrhosis. To date, our study is the only study which provides information on the anticoagulant effect of edoxaban in patient with CTP A cirrhosis. All patients with cirrhosis regardless of their disease severity, are hypercoagulable.(6) This might argue for a reassessment of the careful dosing regimens that currently are used.