Describe the functions and deficiency of vitamin K. Explain the action of warfarin.

Nature and Sources

• Requirement 50–100 µg/day; largely met by gut flora
• Absorption needs bile salts — hence deficiency in obstructive jaundice

Function — Γ-carboxylation

Glutamate residue in the precursor protein → γ-Glutamyl carboxylase, requiring vitamin K and CO2 → γ-Carboxyglutamate (Gla) → Gla residues chelate Ca2+ → Protein binds to phospholipid membrane → Biologically active

Deficiency

• Bleeding tendency — easy bruising, mucosal bleeding, haematuria
• Prolonged prothrombin time with a normal platelet count and bleeding time
• Causes — newborn (sterile gut, poor placental transfer, low milk content); obstructive jaundice and fat malabsorption; prolonged broad-spectrum antibiotics; liver disease; warfarin
• Haemorrhagic disease of the newborn — bleeding on days 2–5; prevented by 1 mg vitamin K intramuscularly at birth

Warfarin and its Antagonism

Warfarin inhibits vitamin K epoxide reductase → Vitamin K cannot be regenerated from its epoxide → γ-Carboxylation fails → Inactive (des-carboxy) clotting factors — PIVKA → Anticoagulation

• Onset takes 2–3 days, until existing factors are cleared — factor VII has the shortest half-life (6 h) so PT rises first
• Protein C also falls early, which can cause a transient prothrombotic state and warfarin-induced skin necrosis; heparin cover prevents it
• Reversed by vitamin K (slow) or fresh frozen plasma / prothrombin complex concentrate (immediate)

Applied Aspects

• Monitored by prothrombin time expressed as INR; target 2–3 for most indications
• Dietary consistency matters more than avoidance — patients on warfarin should keep their green vegetable intake steady rather than eliminate it
• Vitamin K is contraindicated in pregnancy only as warfarin is — warfarin itself is teratogenic and is replaced by heparin
• Rodenticides (superwarfarins) cause prolonged bleeding requiring weeks of vitamin K treatment