Treatment and prothrombin responses during warfarin toxicosis in rats and mice

Efficacy of whole blood, vitamin K-3 and vitamin K-1 treatment during warfarin feeding was investigated in rats and mice. Prolonged prothrombin times were observed in mice after 9--12 h of warfarin feeding. Prothrombin times greater than 300 sec were consistently observed in mice on continuous warfarin feeding and receiving whole blood or vitamin K-3 treatment. Withdrawal of warfarin resulted in normal prothrombin times after 96 h in mice receiving no treatment, 48--72 h on whole blood and 48 h in mice treated with 72 mg vitamin K-3/kg of body wt./day. Marked protection against warfarin induced hypoprothrombinemia and mortality occurred in mice treated with 5 mg vitamin K-1/kg/day. Treatment with 72 mg vitamin K-1/kg/day resulted in rapid alleviation of hypoprothrombinemia and prolonged protection against warfarin toxicosis. Intraperitoneal administration of 72 mg/kg/day of vitamin K-1 or vitamin K-3 were not toxic to mice. Mortality was consistently higher in mice given warfarin continually and in those receiving the greater number of treatments. Frequent handling appears to aggrevate warfarin toxicosis.