Influence of warfarin therapy on activated factor VII clotting activity

Oral anticoagulant therapy has been widely employed to prevent and treat a variety of thrombotic disorders, although a new generation of antithrombotic drugs, which offer inhibition of clot-bound as well as fluid-phase thrombin, has been developed and tested in several clinical trials. Although most anticoagulant responses to hydroxycoumarin compounds are well established, there are controversial evidences on their influence on activated factor VII (FVIIa). After analyzing the prothrombin time (PT) (International Normalized Ratio reference range, 0.92-1.08), factor VII clotting activity (FVII:C) (reference range, 75-130 U/dl) and activated factor VII clotting activity (FVIIa:C) (reference range, 30-110 U/l) in 46 consecutive patients on stable warfarin therapy for atrial fibrillation, a consistent trend towards decreased values of both FVII:C and FVIIa:C was observed as PT values increased. At moderate-intensity anticoagulation, with international normalized ratios between 2 and 3, the mean activities of FVII:C and FVIIa:C dropped to 28 U/dl (range, 9-61 U/dl) and 5.8 U/l (range, 1-18 U/l), respectively. Results of our investigations indicate that warfarin therapy decreases FVIIa:C, highlighting the potential benefits of oral anticoagulants in thrombotic disorders and other clinical conditions characterized by increased levels of FVIIa. Owing to the good correlation with FVIIa:C, we also hypothesize that the PT and/or FVII:C might be employed for monitoring recombinant FVIIa therapy.