Hemostasis and anticoagulant therapy in liver diseases

Hemostasis is a complex process to stop bleeding from damaged blood vessels. A disturbance in the hemostatic system may result in either a bleeding or a thrombotic tendency. The liver plays a central role in the hemostatic system as it synthesizes the majority of hemostatic proteins. There are, therefore, profound changes in the hemostasis of patients with liver disease. Historically, these changes were interpreted as predisposing for a bleeding tendency. Nowadays, however, we know that patients with a liver disease are at risk for both bleeding and thrombosis. Studies in this thesis deal with an in depth understanding of the hemostatic system in patients with liver disease. Additional evidence for the concept of ‘rebalanced hemostasis’ in patients with specific liver diseases is provided. Thrombotic complications are increasingly diagnosed in patients with liver disease. However, little research has been done on the efficacy and safety of the available anticoagulant drugs in patients with liver disease. Therefore, guidelines on the anticoagulant drug of choice and dosing for the various indications are still lacking. Studies described in this thesis assessed the efficacy and monitoring of anticoagulant drugs in plasma from patients with liver disease. In short, we found that the anticoagulant potency of clinically approved drugs differs substantially between patients with chronic liver disease and healthy individuals. Drug-specific dose adjustments may, therefore, be required in these patients. The results of this thesis contribute to development of better strategies to prevent or treat thrombosis in patients with liver disease