Response to warfarin in hypothyroid rats

Abstract

Effects of a single intravenous dose of warfarin in thyroidectomized rats were compared with responses of sham-neck operated, euthyroid and control rats. Control prothrombin times were similar in thyroidectomized and control rats. Prolongation of the one-stage prothrombin time after warfarin was less at 24 hr in the thyroidectomized rats than in the control rats. However, if the prothrombin response was examined over the duration of its effect, the response to warfarin was significantly greater in the thyroidectomized rats; plasma half-life of warfarin was significantly longer in thyroidectomized rats. No differences were noted in the calculated volumes of distribution, the plasma protein binding of warfarin, or in the total plasma protein and plasma albumin concentrations between thyroidectomized and control rats. These findings emphasize the point that the hypoprothrombinemic effects of indirect anticoagulants must be followed over the entire period of increased prothrombin time in order to reach valid conclusions about the interference of disease, simultaneously administered drugs, genetic and other factors. We conclude that hypothyroid rats are not resistant to the anticoagulant effect of warfarin, as previously reported, but actually are more sensitive than are normal rats.