**1. Introduction**

The liver is the largest organ in the body, and while it only accounts for about 3% of the total body weight it receives 25% [1, 2] of the cardiac output via the hepatic artery and portal vein. This is due to its multifunctionality in regulating glucose and amino acid homeostasis, detoxifying the blood, processing of lipoproteins and their fats, synthesis of bile and proteins, storage of glycogen and vitamins and filtering of bacteria, etc.

Hepatocytes produce many of the proteins involved in normal regulation of the clotting cascade and fibrinolytic system. These, with platelets, achieve a balanced haemostasis system with fine controls and checks at many levels to maintain free flow of blood within the circulation, prevent uncontrolled clotting of the blood and quickly plug blood vessel wall breaches to limit blood loss. Toxins and pathogens can not only cause hepatocyte injury but also damage hepatic sinusoidal cells and endothelial cells (ECs) throughout the circulation. The injury results in reduced synthesis of clotting factors but due to compensating changes in additional factors that regulate the clotting and fibrinolytic cascades, haemostasis and thrombin generation remain

in balance [3] and any bleeding is usually due to the presence of varices. This new haemostasis balance is more sensitive to perturbation because synthesis and release of proteins and proteases responsible for its fine tuning, that come not only from hepatocytes but also sinusoidal cells and ECs, are also disrupted. The initial result is more likely to be a procoagulant state, but if hepatic dysfunction worsens the balance may tip the other way with predomination of fibrinolysis, thrombocytopenia and worsening platelet dysfunction causing bleeding.
