Cofactor for gamma-carboxylation of factors II, VII, IX and X plus proteins C and S
Expansion
Vitamin K is the cofactor for gamma-carboxylation of glutamate residues, which allows these factors to bind calcium and phospholipid surfaces. Without it they are synthesised but non-functional.
Vitamin K dependent factors: II, VII, IX and X (the 1972 mnemonic), plus protein C and protein S, and osteocalcin in bone.
Sources: green leafy vegetables (K1) and colonic bacteria (K2).
Deficiency
- Newborns: low placental transfer, low milk content and a sterile gut, causing haemorrhagic disease of the newborn. Prevented by intramuscular vitamin K at birth
- Fat malabsorption and cholestasis
- Prolonged broad-spectrum antibiotics, killing the gut flora
- Warfarin
Warfarin inhibits vitamin K epoxide reductase, preventing regeneration of the active cofactor. Two consequences follow: the effect is delayed until existing factors clear, with factor VII falling first; and because protein C also has a short half life, there is transient hypercoagulability, which is the mechanism of warfarin-induced skin necrosis.
Reversal is with vitamin K (slow) or prothrombin complex concentrate (immediate).