The liver is a central organ in the hemostatic system as it is the site of synthesis of many proteins involved in the activation and regulation of coagulation and fibrinolysis. In addition, the liver synthesizes thrombopoietin, which is a key hormone involved in the production of platelets. Patients with advanced chronic liver disease or acute liver failure develop alterations in their hemostatic system that are at least partly related to decreased synthetic capacity of the diseased liver. In addition, hemostatic changes in patients with liver disease may be related to systemic or intrahepatic activation of coagulation with consumption of hemostatic components. Finally, chronic endothelial cell activation resulting in elevated levels of endothelial-derived proteins such as von Willebrand factor contributes to the hemostatic changes associated with liver disease.
Although historically liver diseases were considered as bleeding disorders, nowadays it is recognized that liver diseases are not only associated with bleeding but also with thrombotic complications. Because of the absence of high-quality clinical evidence, it is still unclear how to best prevent or treat bleeding and thrombosis in patients with liver diseases. The combination of laboratory studies with clinical observations, however, has led to a more rational approach to hemostatic management. In recent years, a number of international societies have issued clinical guidance documents in this area that share a number of concepts. First, the concept of rebalanced hemostasis has become widely embraced. The recognition that patients with liver disease have concomitant changes in both prohemostatic and antihemostatic systems leading to a relatively preserved hemostatic system has led to a much more restrictive approach to prophylactic correction of hemostasis with the aim to prevent bleeding, for example, before invasive procedures. It is now widely accepted that routine diagnostic tests of hemostasis, such as the platelet count and the prothrombin time, are unsuitable as indicators of hemostatic capacity in patients with cirrhosis. As a consequence, routine prophylactic correction of a low platelet count and a prolonged prothrombin time by infusion of platelet concentrates or fresh frozen plasma is increasingly discouraged. Second, the recognition of a hypercoagulable state in patients with cirrhosis, for example evidenced by enhanced in vitro thrombin generating capacity and an elevated risk for development of venous thromboembolism, has led to increased awareness for the role of thromboprophylaxis, even in those patients with thrombocytopenia and/or prolonged prothrombin time.
Here, the author outlines the recent developments in the prevention and management of bleeding and thrombosis in patients with liver disease.