In liver failure all clotting factors are low, except for factor VIII which is paradoxically supra-normal. This is because factor VIII is synthesised in endothelial cells throughout the body, unlike the other clotting factors which are synthesised purely in hepatic endothelial cells. Furthermore, whilst activated factor VIII is usually rapidly cleared from the blood stream, good hepatic function is required for this to occur, further leading to increases in circulating factor VIII. This is one of many reasons why, despite conventional coagulation studies (increased PT, APTT, decreased fibrinogen) suggesting increased bleeding risk, patients with chronic liver disease are not protected from venous thrombosis formation but are paradoxically at an increased risk of thrombosis, in addition to bleeding.
Other events occurring in chronic liver disease which predispose patients to thrombosis formation include reduced synthesis of the purely hepatic derived natural anticoagulants protein c and protein s (vitamin k dependent), and anti-thrombin (non-vitamin k dependent).