Coagulopathy in liver diseases: complication or therapy?

Coagulopathy in cirrhosis is a composite condition where liver synthetic deficit rebalances coagulation to a parallel reduction of both pro- and anticoagulant factors. Cirrhosis is therefore no longer considered a hypocoagulable state but rather a more unstable hemostatic balance with a lower threshold for tipping toward thrombosis or bleeding. Tendency to bleeding in cirrhosis is due to the reduction in the synthesis of procoagulants and a low platelet count as well as hyperfibrinolysis. Variceal hemorrhage is a frequent bleeding complication in decompensated cirrhosis. However, the possible contribution of coagulopathy as a precipitant or an aggravating factor is poorly documented and further data are required to clarify its real contributing role. Moreover, apart from the gastrointestinal tract, the occurrence of spontaneous and procedure-related bleeding elsewhere in the body, whilst not uncommon, is less than would be expected. By contrast, a large-scale population-based study has shown the propensity towards venous thrombosis in patients with liver diseases. Portal vein thrombosis (PVT) is a critical but frequent event occurring in up to 40% of patients with liver cirrhosis. PVT causes deterioration of the clinical course, the complications of portal hypertension and an increase in post-transplant mortality. The pathogenesis of PVT includes both local alterations, like blood flow reduction and endothelial activation, and systemic derangement. Systemic prohemostatic alterations include high von Willebrand factor, low ADAMTS-13, low levels of anticoagulants (antithrombin, proteins C and S) and increases in procoagulants like factor VIII. Low-molecular-weight heparin such as enoxaparin has proven to be safe and effective in both the treatment and prevention of PVT. In addition, patients in prophylaxis with enoxaparin showed a lower rate of decompensation and a better survival without bleeding complications. In such patients, circulating bacterial DNA, endotoxemia and markers of inflammation were attenuated compared to controls. These results therefore suggest a possible connection between enoxaparin, decrease of endotoxemia and reduction of portal hypertension. The approach to the coagulopathy in patients with liver diseases is changing: while the main goal for clinicians so far has been to reduce the risk of bleeding, the results of these new studies highlight the importance of preventing or treating thrombophilic disorders like PVT to avoid microcirculatory damage and eventually liver decompensation.