Sarah Bos

45 Changes of in vitro potency of anticoagulant drugs 3 Discussion In this study we assessed the anticoagulant potency of 3 classes of anticoagulant drugs in patients with mild cirrhosis due to NASH or ASH. In line with our previous study,(4) we found a profoundly increased anticoagulant response of dabigatran in patients with cirrhosis. No clear differences in anticoagulant response between controls and patients were found for apixaban and LMWH, which is also in line with our previous study, in which we only found an enhanced anticoagulant effect of a direct Xa inhibitor in patients with more advanced disease and only found an enhanced anticoagulant effect of LMWH in cirrhosis when we used thrombin generation in the absence of thrombomodulin.(4) Thus, in patients withmild disease, the anticoagulant potency of LMWHor apixaban is not different from that in controls, regardless of the etiology of disease. This is in line with increasing clinical studies on the safety of LMWH and direct Xa inhibitors in patients with mild to moderate cirrhosis.(13–15) The profoundly enhanced anticoagulant effect of dabigatran, however, suggests the need for further study of this drug, even in patients with mild hepatic impairment. We did not observe an altered in vitro anticoagulant potency of anticoagulants between patients with NASH or ASH-related cirrhosis. However, dabigatran did appear to exert a larger anticoagulant effect in plasma from patients with ASH- related cirrhosis compared to NASH-related cirrhosis. As this difference may be explained by the slightly higher MELD score in patients with ASH-related cirrhosis, this warrants further study. Notably, a comprehensive profile of the hemostatic status of these patients revealed very few differences between patients with NASH- and ASH-related cirrhosis.(16) These findings contrast the concept that NASH-related cirrhosis is associated with an hypercoagulable profile compared to liver diseases of other etiologies. Rather, our results are consistent with the notion that the surplus of thrombotic events in NASH-related cirrhosis is caused by cardiometabolic risk factors and features of the metabolic syndrome, and not directly by a hypercoagulable state.(7,8,16) In conclusion, this study confirms previous findings on an enhanced in vitro potency of dabigatran in patients with cirrhosis and a similar in vitro anticoagulant potency of apixaban and enoxaparin in patients with mild cirrhotic disease. Our study does not suggest differences in in vitro anticoagulant potency of these commonly used classes of drugs between patients with different etiologies of disease. Collectively, the results emphasize the need for further assessment of in vivo potency and safety of anticoagulation in cirrhosis