Potentiation by glucagon of the hypoprothrombinemic action of warfarin.

Hospitalized patients treated with warfarin were monitored to identify additional drugs that modify its hypoprothrombinemic action. Twenty-four patients on warfarin therapy received glucagon in daily doses from 2 to 96 mg for treatment of myocardial contractile failure. Eight of nine patients who were given glucagon for 2 or more days in a total dose exceeding 50 mg showed marked enhancement of the hypoprothrombinemic effect of warfarin. In these patients the ratio of prolongation of the one-stage prothrombin time to total warfarin dose during the preceding 72 hr increased three- to twelvefold on glucagon therapy. All patients became excessively hypoprothrombinemic, and three bled while on both warfarin and glucagon. Glucagon does not significantly prolong the prothrombin time in patients not receiving oral anticoagulants. Glucagon may potentiate the hypoprothrombinemic action of warfarin by acting synergistically with the anticoagulant to depress hepatic synthesis of vitamin-K-sensitive clotting proteins or by increasing the affinity of warfarin for its receptor site. [ABSTRACT FROM AUTHOR]