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The effect of vitamin K1 on the response of 6 healthy volunteers to the anticoagulant, warfarin, was measured. When warfarin (40 mg.) and vitamin K1 (1 mg.) were administered simultaneously, there was a marked variation between individuals in the ability of the vitamin to antagonize the anticoagulant effect. One subject showed no antagonism; two showed complete antagonism; others showed an intermediate response. When vitamin K1 was administered 24 hours prior to warfarin, less variation was noted between individuals. One subject continued to show no antagonism; the others showed an intermediate effect. When vitamin K1 was administered 48 hours after warfarin, at the height of the anticoagulant response, there was a marked variation between individuals in the time required for clotting activity to return to normal. Two subjects appeared to synthesize or release vitamin K-dependent clotting factors rapidly; another subject appeared to synthesize or release it slowly; and others released it at an intermediate rate. These experiments indicate that there is considerable variation in the normal population in response to vitamin K1 and suggest that this variation is due to a number of factors: differences in rates of metabolism or excretion of vitamin K1, differences in receptor site affinity in the liver for vitamin K1, and differences in the rate of synthesis or release of vitamin K-dependent clotting factors.
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Accepted: October 1, 1968
Received: August 1, 1968
© 1969 Published by Elsevier Inc.