Carboxylation of vitamin K–dependent proteins requires the reduced form of vitamin K, γ-glutamyl carboxylase enzyme, molecular oxygen, and carbon dioxide. Carboxylation of vitamin K–dependent proteins requires the reduced form of vitamin K, γ-glutamyl carboxylase enzyme, molecular oxygen, and carbon dioxide. Because body stores of vitamin K are low, the oxidized (inactive) form of vitamin K is recycled to the reduced (active) form by vitamin K epoxide reductase, which is inhibited by warfarin. Inhibition results in reduced hepatic synthesis of these clotting factors and reduction in their activities by 40%–50%. Nishank Jain, and Robert F. Reilly CJASN 2019;14:278-287 ©2019 by American Society of Nephrology