Vitamin K is required for a liver microsomal enzyme that catalyzes the posttranslational conversion of specific glutamyl residues in precursors of the vitamin K-dependent clotting factors to gamma-carboxyglutamyl residues in the plasma form of these proteins. A second product of this carboxylation reaction is the 2,3-epoxide of the vitamin. The anticoagulant warfarin blocks the enzyme which reduces this epoxide to vitamin K quinone, and also blocks one of the microsomal pathways which converts the quinone to the active coenzyme form of the vitamin, the hydroquinone. Warfarin anticoagulation therefore reduces the activity of the vitamin K-dependent carboxylase and results in the secretion of vitamin K-dependent clotting factors that are under carboxylated. The presence of gamma-carboxyglutamyl residues is essential for the normal Ca++/phospholipid-mediated activation of prothrombin, and the des-gamma-carboxy forms of prothrombin secreted by patients receiving warfarin therapy lack biological activity and have a reduced thrombotic potential.