Clotting Factors Not Produced by the Liver
Factor VIII and von Willebrand factor (vWF) are the only clotting factors not produced by the liver. While most coagulation factors are synthesized by hepatocytes, factor VIII is produced by liver sinusoidal endothelial cells, and vWF is produced by endothelial cells throughout the body 1, 2.
Liver-Produced Coagulation Factors
The liver is responsible for the synthesis of most blood coagulation factors:
- Fibrinogen (Factor I) 1
- Prothrombin (Factor II) 1
- Factor V 1
- Factor VII 1
- Factor IX (Christmas factor) 1, 3
- Factor X 1
- Factor XI 1
- Factor XII 1
- Protein C 1
- Protein S 1
- Antithrombin 1
Non-Liver Produced Coagulation Factors
- Factor VIII: While early studies suggested the liver as a major site of synthesis, more recent evidence has demonstrated that factor VIII is primarily produced by liver sinusoidal endothelial cells rather than hepatocytes 2
- von Willebrand factor (vWF): Produced by endothelial cells throughout the body and by megakaryocytes 1, 4
Clinical Implications
Understanding which clotting factors are produced by the liver has important clinical implications:
- In liver disease, there is decreased synthesis of liver-derived procoagulant factors (factors V, VII, X) causing prolongation of prothrombin time 5
- However, liver disease also causes decreased synthesis of anticoagulant factors like protein C, creating a rebalanced but precarious hemostatic state 5
- Factor VIII levels are often elevated in cirrhosis because it's not produced by hepatocytes 5
- vWF is consistently elevated in cirrhosis, which partially compensates for thrombocytopenia by supporting platelet adhesion 5
This understanding explains why traditional coagulation tests like INR have significant limitations in liver disease patients, as they measure only procoagulant factors but not the deficit of liver-derived anticoagulant factors 5, 6.
Diagnostic Considerations
When evaluating coagulation in patients with liver disease:
- Standard coagulation tests (PT/INR) primarily reflect deficiencies in liver-produced factors but don't account for the balanced reduction in both pro- and anticoagulant factors 5
- Elevated Factor VIII and vWF levels in cirrhosis can contribute to a relatively hypercoagulable state despite prolonged INR 5
- This rebalanced hemostasis explains why patients with liver disease often don't have the same bleeding patterns as those with specific coagulation factor deficiencies 6
Understanding the source of different clotting factors helps explain the complex and sometimes paradoxical coagulation profiles seen in patients with liver disease 5.