424 ■ VITAMIN K GROUP 



Since small doses of vitamin K correct the hypoprothrombinemia accom- 

 panying intestinal "sterilization," the possibility of prothrombin changes 

 secondary to hepatic damage would seem to be excluded. However, Bra- 

 ganca and Radhakrishna Rao*^ reported that infiltration with fat de- 

 veloped in the livers of rats after 2 weeks of a diet containing sulfathiazole; 

 this hepatic change was prevented by addition of vitamin K to the sulf on- 

 amide-treated diet. The data of Mushett and Seeler^^ suggest that in 

 sulfonamide hypoprothrombinemia vitamin K] is 100 to 250 times as 

 effective as menadione; by analogy with vitamin K suppression of dicou- 

 marol action, an hepatic site of action might be considered, for in simple 

 vitamin K deficiency states menadione is the more potent. 



Rats develop hypoprothrombinemia when subjected to a diet high in 

 triglycerides containing dihydroxystearic acid.'^^ The clotting change is ac- 

 companied by disappearance of vitamin K from the intestinal contents and 

 is corrected by the administration of the vitamin (0.1 mg. per day). Since 

 the intestinal bacteria are qualitatively and quantitatively normal during 

 the period of vitamin K deficiency, it seems that the vitamin-synthesizing 

 systems of the bacteria are blocked. ^^^ 



c. Reduced Absorption of Vitamin K 



(1) Absence of Bile. Quick et alP first reported blood-clotting changes in 

 human obstructive jaundice comparable to those already demonstrated in 

 vitamin K-deficient chicks. Hawkins and Brinkhous'"' found the same clot- 

 ting condition in experimental biliary fistulas in dogs. The lack of bile in 

 the intestine was common to both states and was soon recognized to be 

 etiologically important in vitamin K deficiency.''^ Fantl and coworkers*''^ 

 have recently questioned this concept. 



In rapid succession Warner et al.f^ Butt et al.,'^^ and Dam and GJavind*'* 

 reported the successful correction of the clotting changes and of the bleed- 



38 C. W. Mushett and A. O. Seeler, /. Pharmacol. Exptl. Therap. 91, 84 (1947). 



38a E. E. Lockhart, H. Sherman, and R. S. Harris, Science [N. S.] 96, 542 (1942). 

 38b G. Nightingale, E. E. Lockhart, and R. S. Harris, Arch. Biochern. 12, 381 (1947). 



39 A. J. Quick, M. Stanley-Brown, and F. W. Bancroft, Am. J. Med. Sci. 190, 501 

 (1935). 



" W. B. Hawkins and K. M. Brinkhous, J. Exptl. Med. 63, 795 (1936). 



^' H. P. Smith, E. D. Warner, K. M. Brinkhous, and W. H. Seegers, J. Exptl. Med. 



67, 911 (1938). 

 "a p. Fantl, J. F. Nelson, and G. J. Lincoln, Australian J. Exptl. Biol. Med. Sci. 29, 



433 (1951). 

 « E. D. Warner, K. M. Brinkhous, and H. P. Smith, Proc. Soc. Exptl. Biol. Med. 37, 



628 (1938). 

 « H. R. Butt, A. M. Snell, and A. E. Osterberg, Proc. Staff Meetings Maijo Clinic 13, 



74 (1938). 

 "H. Dam and J. Glavind, Lancet I, 720 (1938). 



