Sarah Bos

20 CHAPTER 2 Abstract Background: patients with cirrhosis may acquire profound changes in hemostasis. Although hemostatic changes in cirrhosis have been extensively studied, most studies were performed in groups of patients with mixed etiology. As thrombotic events appear more common in some etiologies of disease, notably non-alcoholic steatohepatitis (NASH) and cholestatic disease, we hypothesized that hemostatic changes might be different across etiologies. Methods: we studied 109 patients with cirrhosis (31 cholestatic liver disease, 23 NASH, 37 alcoholic liver disease (ALD), 18 viral hepatitis) and 44 healthy controls. Patients with malignancy were excluded. Routine diagnostic tests of hemostasis, thrombin generation assays, fibrin permeability assays, and a plasma-based fibrinolytic assay were performed. Results: all patients had comparable severity of disease according to their MELD- score(9 [7-11]). Plasma levels of von Willebrand factor were substantially elevated across all etiologies, with ADAMTS13 levels comparable to controls. Thrombin generation capacity was elevated in all etiologies, most profoundly in ALD. Fibrin permeability was decreased in all etiologies, which was accompanied by elevated fibrinogen levels. Clot lysis times were prolonged in NASH and cholestatic disease. Plasma levels of individual proteins were similarly altered in all etiologies. Conclusion: our in-depth hemostatic profiling of primary, secondary, and tertiary hemostasis inagroupof patientswithCPTA/Bcirrhosis showedno largedifferences between etiologies, and was consistent with a general hypercoagulable profile in patients with mild cirrhosis. These results suggest that patients with cirrhosis have an increased risk of thrombosis, irrespective of their etiology.