Sarah Bos

121 General discussion 7 There are multiple other results from this study cohort that are of interest. The thrombomodulin modified thrombin generation that was used, comprises all major pro- and anticoagulant proteins. Our cohort showed, in agreement with the latest literature, an enhanced thrombin generating capacity.(5,6,9,11) There seems to be some slight differences in the endogenous thrombin potential between some of the etiologies of cirrhosis. More detailed testing of levels of pro- and anticoagulant proteins did not explain these slight differences. Possibly other unknown factors that influence hemostasis explain the possible differences between etiologies. Even though the PT and all the individual plasma levels of coagulation factors were similar between all etiologies, there was an increase in the activated partial thromboplastin time (aPTT) in patients with cholestatic disease and viral hepatitis. None of the levels of the individual procoagulant or anticoagulant proteins could explain these differences in aPTT. Effect of in vitro anticoagulants in patients with cirrhosis Since patients with cirrhosis have profound and complex changes in their hemostatic system, it is conceivable that pro- and anticoagulant drugs have altered pro- or anticoagulant effects in these patients. A first step in the assessment of the efficacy of anticoagulant drugs in patients with cirrhosis are in vitro studies. In chapter 3 the anticoagulant potency of 3 classes of anticoagulant drugs in patients with mild cirrhosis due to non-alcoholic steatohepatitis (NASH) or alcoholic steatohepatitis (ASH) were studied. We found that in patients with CTP A/B cirrhosis, the anticoagulant potency of low molecular weight heparin (LMWH) or apixaban in NASH cirrhosis and ASH cirrhosis is not different from that in controls. These findings are supported by increasing evidence of clinical studies on the efficacy and safety effect of LMWH and direct Xa-inhibitors in patients with CTP A/B cirrhosis.(13–16) In contrast to the similar effect of LMWH and apixaban in both NASH and ASH cirrhosis, dabigatran had a stronger in vitro anticoagulant effect in the plasma of patients with ASH cirrhosis compared to NASH-related cirrhosis. The only clinical difference between these groups that might influence these results, is the difference in MELD-score which is higher in the group of patients with ASH related cirrhosis. As was shown in chapter 2, on a detailed hemostatic level there are no significant differences between NASH and ASH cirrhosis. An earlier study which also tested the hemostatic status of NASH and ASH cirrhosis patients in detail supported the findings of chapter 2.(17) In contrast to these results, a recent retrospective cohort study among nearly 9000 patients with NASH or ASH cirrhosis showed an increased incidence of portal vein thrombosis (PVT) in NASH cirrhosis