Bleeding and Thrombosis in Patients with Liver Diseases

Patients with liver disease acquire substantial changes in their hemostatic system. While historically these changes were interpreted as indicating a bleeding tendency, we now understand that patients with liver disease-associated hemostatic changes do not have a “coagulopathy.” Rather, the simultaneous decrease in proand antihemostatic drivers results in a rebalanced hemostatic status.1,2 It has been postulated that the fragile hemostatic balance can easily be tipped toward a hypoor hypercoagulable state, which explains the occurrence of both bleeding and thrombotic complications. However, a substantial proportion of bleeding complications in patients with cirrhosis are likely unrelated to hemostatic failure but rather relate to portal hypertension or mechanical injury to vessels, for example, in variceal bleeding and laceration of vessels during invasive procedures. Thus, over the last two decades, the hemostatic concerns in patients with liver diseases have shifted from a real concern for bleeding and major attempts to improve hemostasis by prophylactic use of blood products and other hemostatic agents to a concern for thrombosis, with increasing attention for the optimal use of anticoagulant therapy.3–7 In this issue of Seminars in Thrombosis and Hemostasis, we highlight new developments in the broad context of the prevention and management of bleeding and thrombosis in patientswith liver diseases. Although, unfortunately, highquality clinical evidence to guide hemostatic management is still lacking, there is accumulating lower quality evidence and increasing clinical experience to support the development of rational management advice. The issue starts with a contribution of Roberts and Bernal who review the magnitude of bleeding and thrombotic complications in patientswith acute and chronic liver failure, with a focus on spontaneous bleeding and bleeding associated with invasive procedures including liver transplant surgery.8 The authors emphasize that bleeding complications in patients with cirrhosis are common but often appear unrelated to the coagulopathyof liver disease. Also, the challenges in the prevention and treatment of thrombotic complications such as deep vein thrombosis, pulmonary embolism, and portal vein thrombosis are discussed. Subsequently, Northup and Davis discuss shortcomings in clinical studies on the prevention and management of bleeding and thrombosis and provide recommendations for future studies.9 The authors stress the importance of clear and validated clinical end points, proper sample sizes, and multicenter and multidisciplinary efforts to take this field forward. Next, NicoarăFarcău et al discuss new insights into the pathogenesis and management of cirrhotic portal vein thrombosis.10 Portal vein thrombosis is a common complication of cirrhosis, but whether (asymptomatic) portal vein thrombosis is just a “predictable milestone” of cirrhosis or an active driver of disease progression continues to be debated, and, hence, if and who qualifies for active treatment is not fully established. The authors summarize their approach and indicate areas in which additional studies are required. A paper by Khemichian and Terrault discusses the use of thrombopoietin receptor agonists in patients with cirrhosis.11 Although there is increasing consensus that the correction of a prolonged international normalized ratio in patients with cirrhosis prior to procedures is not required, there is no consensus on how to handle cirrhotic thrombocytopenia in the context of procedures. Khemichian and Terrault review evidence on efficacy and safety of thrombopoietin receptor agonists in cirrhosis and demonstrate that these agents effectively increase platelet count without major side effects, but there is little evidence that they reduce procedural bleeding.