Sarah Bos

21 Hemostatic profiles are similar across all etiologies of cirrhosis. 2 Introduction Historically, patients with cirrhosis were considered to be prone to bleeding complications due to their acquired coagulopathy. The hemostatic profile in cirrhosis is characterized by decreased levels of most pro-coagulant factors. However, the decrease in plasma levels of procoagulant factors is paralleled by a decrease in plasma levels of most of the natural anticoagulants including antithrombin, protein C and protein S.(1) Similarly, decreased plasma levels of antifibrinolytic proteins are accompanied by decreased plasma levels of plasminogen.(2) Furthermore, the thrombocytopenia of cirrhosis appears to be counteracted by highly elevated levels of the platelet adhesive protein von Willebrand factor (VWF).(3) The net effect of all these changes in the pro- and antihemostatic pathways appears to be a reset of the hemostatic balance.(2) This restored hemostatic balance, however, is fragile and can easily be tipped towards a hypo- or hypercoagulable status.(2) Indeed, both bleeding and thrombotic events are common in cirrhosis, although it remains a challenge to predict which patient is at risk for thrombotic or hemorrhagic complications. Recent studies have demonstrated that cirrhosis is actually a risk factor for development of venous thromboembolism.(4–8) Laboratory data in support of a maintained hemostatic balance in cirrhosis includes studies showing that thrombin generating capacity of patients with cirrhosis is normal or even enhanced compared to healthy individuals,(6–9) data that show a preserved fibrinolytic balance,(2) and studies showing that a highly elevated VWF levels compensate for cirrhotic thrombocytopenia.(3,10) Most laboratory studies that assessed different aspects of hemostatic balance in cirrhosis have been performed using patient cohorts with mixed etiologies. However, clinically, there appear to be differences in hemostatic complications between different etiologies of disease. For example, it has been well established that patients with cholestatic disease display increased hypercoagulability by viscoelastic tests,(11–14), and anecdotally, patients with cholestatic disease appear to have decreasedblood loss during liver transplantation. It has not been establishedwhether patients with cholestatic disease are at increased risk for thrombotic complications. Two independent laboratory studies have demonstrated little differences between patients with cirrhosis due to NASH, alcohol or viral hepatitis, although specific hypercoagulable features of NASH were identified in one of these studies.(14,15) However, hospitalized patients with cirrhosis due to NASH were at increased risk for venous thrombosis compared to patients with cirrhosis of other etiologies.(16) In line with this clinical evidence for a (relative) hypercoagulable state in patients with NASH- cirrhosis, it has been demonstrated that portal vein thrombosis is more frequent in NASH-cirrhosis compared to cirrhosis of other etiologies.(17)