Blood level of which clotting factor declines most rapidly after the initiation of warfarin therapy

WARFARIN(oral anticoagulant) Mech of action:- They act indirectly by interfering with the synthesis of vit K dependent clotting factors in liver. They apparently behave as competitive antagonists of vit K and lower the plasma levels of functional clotting factors in a dose-dependent manner. In fact, they inhibit the enzyme vit K epoxidereductase (VKOR) and interfere with regeneration of the active hydroquinone form of vit K. which acts as a cofactor for the enzyme g-glutamyl carboxylase that carries out the final step of g carboxylating glutamate residues of prothrombin and factors VII, IX and X. Factor VII has the shoest plasma t 1/2 (6 hr), its level falls first when warfarin is given, followed by factor IX (t 1/2 24 hr), factor X (t 1/2 40 hr) and prothrombin (t 1/2 60 hr). Though the synthesis of clotting factors diminishes within 2-4 hours of warfarin administration, anticoagulant effect develops gradually over the next 1-3 days as the levels of the clotting factors already present in plasma decline progressively. Ref:- kd tripathi; pg num:-620,621