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Hemostasis in Liver Disease
Liver disease is associated with multiple hemostatic defects leading to both hemorrhagic and thrombotic manifestations. Its effect on coagulation factors, endogenous anticoagulants, and platelets results in rebalanced hemostasis and creates challenging clinical scenarios requiring careful management.
Decreased Synthesis of Pro- and Anticoagulant Factors
All coagulation factors (except FVIII and von Willebrand factor [VWF]) are synthesized in hepatocytes and can be deficient in chronic liver disease. FVIII and VWF are often elevated due to their increased production in endothelium. In the setting of acute liver failure, the rate of development of a coagulation factor deficiency is directly proportional to its half-life in plasma. Because FVII has the shortest half-life (approximately 4–5 hours) of all coagulation factors, patients with acute liver failure develop FVII deficiency before levels of other coagulation factors fall. Components of the common pathway of coagulation also have relatively short half-lives and become deficient next. Because of more pronounced deficiency of FVII and the factors involved in the common coagulation pathway, liver failure tends to have a greater effect on the prothrombin time (PT) compared with the partial thromboplastin time (PTT). FVIII, VWF, and fibrinogen are all acute phase reactants that are usually elevated early in liver failure, but as it progresses, fibrinogen falls due to decreased hepatic production while FVIII and VWF levels remain normal or high.
The liver also synthesizes proteins that inhibit coagulation, such as protein C, protein S, and antithrombin. Deficiency of these proteins likely counteracts shortage of procoagulant factors. This helps maintain hemostasis but can also lead to inappropriate thrombosis.
Vitamin K Deficiency
In patients with cirrhosis and obstructive jaundice, decreased bile salt production and/or delivery can cause decreased absorption of fat-soluble vitamins in the small intestine, including vitamin K, an essential cofactor for the production of biologically active factors II, VII, IX, and X, as well as protein C and S. Prolonged antibiotic use, which inhibits the gut flora that produces Vitamin K, and severe dietary deficiency, as may occur in cases of starvation (usually medically induced) or alcoholic cirrhosis with continued alcohol abuse, may also contribute to a deficiency of vitamin K.
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