Clinicians often regard patients with advanced liver disease as prone to bleeding. Today’s discussion will explore recent data which redefine the magnitude of the bleeding diathesis in patients with advanced cirrhosis and acute liver failure (ALF), and will explore mechanisms of “re-balanced hemostasis,” a relatively new concept in which patients re-establish a neutral state of hemostasis by compensatory mechanisms. Bleeding complications of portal hypertension will not be considered, since they occur as a consequence of hydrostatic pressure and wall tension within blood vessels rather than defective hemostasis.

Although the INR detects deficiencies in liver-derived, pro-hemostatic factors, it provides unreliable information to estimate bleeding risk in patients with liver disease. Thus, the concept of “autoanticoagulation,” the notion that patients with liver failure are prone to bleed and protected from venous thromboembolism by virtue of elevated INR, has been strongly refuted. The platelet count, however, is a more accurate predictor of bleeding complications, and in vitro and clinical studies suggest that a platelet count of >60x109/L is sufficient to support thrombin generation at the 90th percentile of normal, which may be a goal of correction.

The general mechanism of re-balanced hemostasis in liver disease can be at least partially explained by 2 important concepts: (1) liver-derived pro- and anti-coagulant proteins are decreased in parallel, and (2) endothelial-derived hemostatic factors (factor VIII and vonWillebrand factor) are released in response to systemic inflammation, and compensate (perhaps over-compensate) for deficient liver-derived pro-hemostatic factors and platelets, respectively.