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Effects of Vitamin K Deficiency, Warfarin, and Inhibitors of Protein Synthesis upon the Plasma Levels of Vitamin K-dependent Clotting Factors in the Chick¹

Department of Biochemistry, St. Louis University School of Medicine, St. Louis, Missouri 63104

Two-week-old chicks adequate in vitamin K showed a relative lack of vitamin K-dependent clotting factors when compared with the rat, cow, and man. Chick prothrombin was 50%, IX 8%, and X 6% of respective levels in the rat. Factor VII was not detectable in chick plasma. When 1-day-old chicks were fed a vitamin K-deficient diet, prothrombin levels fell to 5% in 5 days, whereas factors IX and X fell to only 60% of normal. After warfarin administration to normal chicks, prothrombin levels fell to 20% in 6 hours, whereas factors IX and X fell to 60%. When cycloheximide was given to normal chicks, all vitamin K-dependent factors fell at the same relative rate with a half time of 2 hours. Cycloheximide also completely blocked the effect of physiological doses (10 µg) of phylloquinone upon prothrombin synthesis, but only partially blocked the effect of pharmacological doses (2.5 mg) of phylloquinone, suggesting an antagonism between cycloheximide and vitamin K at the ribosomal level. Puromycin was effective in blocking the action of vitamin K at both physiological and pharmacological doses. In the chick, unlike the rat, it appears that (1) cycloheximide is fully effective in blocking the action of physiological doses of vitamin K, and (2) the regulatory systems for factors IX and X appear to have a higher affinity for vitamin K and a lower affinity for warfarin than the regulatory system for prothrombin.

KEY WORDS: • vitamin K • phylloquinone • cycloheximide • warfarin • coagulation factors

¹ Supported in part by grant AM 09992 from the National Institutes of Health, United States Public Health Service, Bethesda, Md. 20014.

² Predoctoral fellow of the National Institutes of Health, USPHS. Supported by grant AM 446. Present address: Department of Physiology, Wayne State University School of Medicine, Detroit, Mich. 48201.

³ Postdoctoral fellow of the National Heart Institute, USPHS. Supported by grant 5 FO2 HE 30228 and the Missouri Heart Association. Present address: Pontiac, Ill.

Manuscript received 5 December 1974.