Prevention of bleeding and thrombosis in patients with liver disease

The liver plays a fundamental role in the production and clearance of proteins involved in blood clot formation. Not only does this include proteins that promote blood clotting (prohaemostatic proteins), but also proteins that inhibit this clotting process (antihaemostatic proteins). The scarring of the liver as a result chronic liver diseases, also known as cirrhosis, is therefore associated with complex changes in the haemostatic balance. Historically, this led to the notion that patients with cirrhosis were not only at increased risk of bleeding, but also “auto-anticoagulated”, and thus protected from developing thrombosis. Extensive research using advanced coagulation tests, however, has shown that patients with cirrhosis have a rebalanced, but fragile haemostatic status, with changes in both prohaemostatic and antihaemostatic systems. Consequently, patients with cirrhosis are not only at increased risk of bleeding but also at increased risk of thrombosis. Patients with cirrhosis have however been excluded from major studies investigating the effectiveness of drugs that affect the haemostatic system. Results of a clinical study within this thesis suggest that the efficacy of a single dose of heparin is similar in patients with or without cirrhosis. In addition, the efficacy of platelet inhibitors appears to be similar between patients with cirrhosis and healthy volunteers when added in vitro. Finally, transfusion of prohaemostatic blood products has a mild prohaemostatic effect in patients with cirrhosis, but its effectiveness may not outweigh the risks associated with these transfusions.