Prevention and treatment of hemostatic complications in liver disease

This thesis on the prevention and treatment of hemostatic complications in liver disease starts with a detailed study on the hemostasis in cirrhosis. Our in-depth hemostatic profiling of primary, secondary, and tertiary hemostasis in a group of patients with CPT A/B cirrhosis showed no large differences 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.Whether this translates to a similar effect of anticoagulants was tested in vitro in patients with cirrhosis due to ASH or NASH. Low-molecular-weight-heparin, dabigatran and apixaban were tested and showed no differences on a hemostatic level between groups.For the in vivo testing of anticoagulants we studied the effect of a therapeutic dose of edoxaban in patients and controls. Edoxaban strongly effects the hemostatic activity in patients, but not as much as in controls. Whether this difference translates into a higher risk of thrombosis and necessitates dose-adjustments in patients with cirrhosis should be further assessed.In vitro testing of commonly used anticoagulants in patients undergoing hepato-pancreatico-bilairy surgery showed a profoundly altered efficacy as compared to healthy controls, which may have implications for anticoagulant dosing in the early postoperative period. In the correction of perioperative bleeding complications, prothrombin complex concentrate (PCC) appear much more potent than fresh frozen plasma or recombinant factor VIIa, and PCCs may require conservative dosing and caution in use in patients undergoing HPB surgery