Vitamin K (Phytonadione)

Vitamin K (phytonadione) is an essential, fat-soluble cofactor for γ-carboxylation of clotting factors II, VII, IX, and X, as well as proteins C and S. This post-translational modification allows these proteins to bind calcium and participate in coagulation. In vitamin K deficiency or during warfarin therapy, the liver continues to synthesize these factors, but they are functionally inactive, resulting in impaired thrombin generation and a prolonged INR.

Clinically, vitamin K deficiency may occur in patients with malnutrition, prolonged antibiotic exposure, fat malabsorption, cholestatic liver disease, or critical illness. Neonates are particularly susceptible because of limited hepatic stores and the absence of intestinal flora. Factor VII, which has the shortest half-life, declines first, making INR prolongation an early marker of deficiency.

Intravenous vitamin K is used for warfarin reversal and treatment of vitamin K deficiency, while life-threatening bleeding requires immediate factor replacement with four-factor PCC in addition to vitamin K. Understanding this distinction is critical: PCC replaces factors, whereas vitamin K re-establishes factor production and provides durable correction of the coagulopathy. This is the reason why therapies like KCentra are administered with vitamin K.