Antidotal effect of vitamin K1 against warfarin-induced anticoagulation in horses

Warfarin-induced anticoagulation and reversal of the induced anticoagulation by vitamin K1 were evaluated in 4 mature horses. Each horse was given warfarin IV until the prothrombin (PT) time was prolonged by approximately 1.5 times the predosing base-line value. In experiment 1, we evaluated the time required for PT to return to the predosing value (PT reversal time) after warfarin administration was discontinued. Between each experiment, a 1-week rest period was allowed. In experiment 2, two doses of vitamin K1 (100 mg/dose) were administered IM 6 hours apart, and the PT was monitored hourly for 24 hours. In experiments 3 and 4, the horses were dosed with warfarin as in experiment 1, and the PT reversal time was evaluated after administration of 300- and 500-mg doses of vitamin K1 IM, respectively. In experiment 5, one horse was eliminated from the study, 1 horse was given 300 mg of vitamin K1 IV, and 2 horses were given 300 mg of vitamin K1 subcutaneously (SC); the reversal times were evaluated in the 3 horses given vitamin K1. Therapeutic response time was designated as the time required for the mean PT time of treated horses to reach the midpoint between the longest mean PT time achieved during anticoagulation and the mean base-line PT time. The therapeutic response time, without supportive therapy, after discontinuation of warfarin administration was 30 hours, and there was a PT reversal time of approximately 5 days from the last dose of warfarin. The 100-mg dose of vitamin K1 shortened the therapeutic response time to 12 hours and the PT reversal time to 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)