Clotting Factors Synthesized by the Liver
The liver synthesizes nearly all clotting factors except Factor VIII and von Willebrand factor, which are produced by endothelial cells. 1
Hepatocyte-Synthesized Coagulation Factors
The hepatocytes within the liver are responsible for producing the following clotting factors:
Procoagulant Factors
- Fibrinogen (Factor I) 1
- Prothrombin (Factor II) 1, 2
- Factor V 1, 2
- Factor VII 1
- Factor IX 1, 2
- Factor X 1, 2
- Factor XI 1
- Factor XII 1
Natural Anticoagulants
Fibrinolytic System Components
The liver synthesizes most fibrinolytic factors, though notably not the main activators (t-PA and u-PA, which are produced by endothelial cells). 3
Factors NOT Synthesized by Hepatocytes
Factor VIII (procoagulant activity) and von Willebrand factor are produced by liver sinusoidal endothelial cells and vascular endothelial cells throughout the body, not by hepatocytes. 1, 2 This distinction is clinically important because Factor VIII levels are typically preserved or even elevated in liver disease, unlike other clotting factors that decline with hepatic synthetic dysfunction. 4
Clinical Significance in Liver Disease
When liver disease progresses, defective hepatic synthetic capacity results in decreased plasma levels of the hepatocyte-produced coagulation factors, natural anticoagulants, and fibrinolytic factors. 5, 3 This creates a "rebalanced hemostasis" state where both procoagulant and anticoagulant factors are simultaneously reduced. 4
The vitamin K-dependent factors (II, VII, IX, and X) are particularly sensitive to liver dysfunction and can be further impaired by vitamin K deficiency, which is common in cholestatic liver disease and malnutrition. 2, 6