The Coagulation Defect in Hypervitaminosis A in Rats^[*]

Summary

Rats fed vitamin A, 70 000 u daily for a period of 28 days developed a hemorrhagic state characterized by a prolonged prothrombin time and stypven time, a marked reduction in prothrombin and the factor VII-complex, and an inconstant decrease in factor V activity. A serum defect in thromboplastin generation was also noted. The defects in the extrinsic system were prevented by the simultaneous daily feeding of 60 μg to 120 μg of vitamin K₁ but this did not uniformly prevent the serum defect in thromboplastin generation which is thought to represent a depletion in factor IX.

^* This work was supported by a grant from the Manitoba Heart Foundation.

^** With the technical assistance of Miss E. Friesen and Miss J. Skanderbeg.

• References

• 1 Vedder E. B, Rosenberg C. Concerning the toxicity of vitamin A. J. Nutr 1938; 16: 57
• 2 Harris L. J, Moore T. Hypervitaminosis and vitamin balance. Biochem. J 1928; 22: 1461
• 3 Hart well G. A. Growth and reproduction on synthetic diets. Biochem. J 1927; 21: 1076
• 4 Light R. F, Alscher R. P, Frey C. N. Vitamin A toxicity and hypoprothrombinemia. Science 1944; 100: 225
• 5 Campbell H. A, Smith W. K, Roberts W. L, Link K. P. Studies on the hemorrhagic sweet clover disease. J. biol. Chem 1941; 138: 1
• 6 Walker S. E, Eylenburg E, Moore T. The action of vitamin K in hypervitaminosis A. Biochem. J 1947; 41: 575
• 7 Poole J. C. F. The effects of hypervitaminosis A on blood coagulation in the rat. Quart. J. exp. Physiol 1958; 43: 427
• 8 Rizzo A, Santangelo G. Vitamin A E complesso prothrombinico. Boll. Soc. ital. Biol. sper 1958; 35: 43
• 9 Kommerell B, Berger H. D. über die Veränderungen der Blutgerinnung nach Gaben der Vitamine A. E und B ₆ . Klin. Wschr 1960; 38: 134
• 10 Biggs R, Douglas A. S. The thromboplastin generation test. J. clin. Path 1953; 6: 23
• 11 Bell W. N, Alton H. G. A brain extract as a substitute for platelet suspensions in the thromboplastin generation test. Nature (Lond.) 1954; 174: 880
• 12 Quick A. J. The prothrombin in hemophilia and in obstructive jaundice. J. biol. Chem 1935; 109: 523
• 13 Rapaport S. L, Aas K, Owren P. A. The clotting action of Russell viper venom. Blood 1954; 9: 1185
• 14 Koller F, Loeliger A, Duckert F. Le facteur VII. Rev. Hémat 1952; 7: 156
• 15 Adamis D, Sise H. S, Kimball D. M. The proconvertin test. A simplified method and its application to the study of anticoagulant processes. J. Lab. clin. Med 1956; 47: 320
• 16 Denson K. W. The specific assay of Prower-Stuart factor and factor VII. Acta haemat. (Basel) 1961; 25: 105
• 17 Wolf P. A modification for routine use of Stefaninis’ method of estimation of factor V activity in human oxalated plasma. J. clin. Path 1953; 6: 34
• 18 Bessey O. A, Lowry O. H, Brock M. J, Lopez J. A. The determination of vitamin A and carotene in small quantities of blood serum. J. biol. Chem 1946; 166: 177