762 XII. VITAMINS K 



On the other hand, \'itamin K cannot effect blood clotting when added 

 directly to the l)lood. Thus, Dam ct al^--^^ reported that the vitamin in 

 contact with prothrombin-deficient chick blood did not cause an accelera- 

 tion in clotting time when tested in vitro. Even water-sohible forms such 

 as methj'-lnaphthoquinone, phthiocol, and the diphosphoric acid ester do 

 not influence the rate of clotting when added directly to the blood. ^^ WTien 

 vitamin K is given in an emulsion to deficient chicks, no increase in pro- 

 thrombin occurs immediately; at least fi\e hours are required to restore the 

 prothrombin level to normal. ^^ It is believed that this precludes the possi- 

 bility that vitamin K serves as a prosthetic group in combination with any 

 of the blood elements. 



a. The Liver as the Site of Action of Vitamin K. Since vitamin K is 

 without activity in producing clotting in vitro, and can act only in relation 

 to the animal as a whole, it is believed that it is required in the normal 

 in vivo synthesis of prothrombin. There is considerable evidence that pro- 

 thrombin is synthesized in the liver. It is now agreed that vitamin K 

 must act in this organ to aid in the normal sjmthetic processes. 



The proof that the liver is the site of prothrombin synthesis is based upon 

 a number of different observations. Thus, Andrus and co-workers,^^ 

 and Warren and Rhoads,^^ found that hepatectomy in dogs was followed 

 by a decrease in the blood prothrombin level. When two-thirds of the 

 liver was removed, in rats, a decreased prothombin formation was likewise 

 noted. ^^ An injury to the functional activity of liver tissue has also been 

 shown to reduce the abiUty to synthesize prothrombin. For example, 

 prothrombin formation is impaired after chloroform poisoning,'*-^^ and 

 after traumatic injury to this organ.'"'' In none of these latter cases was 

 vitamin K effective in stimulating the synthesis of prothrombin. Human 

 patients with se\'ere li\er damage failed to respond to the administration of 

 substrates containing vitamin K and bile salts. ^"^ Brinkhous and Walker"" 

 found that the prothrombin concentration in portal lymph is similar to 

 that in the blood, whereas lymph from other sources has lower concentra- 

 tions. This result would support the hypothesis that plasma prothrombin 



96 W. D. Andrus, J. W. Lord, Jr., and R. A. Moore, Surgery, 6, 89iM)00 (1939). 

 9« R. Warren and J. E. Rhoads, Am. J. Med. Sci., 198, 198-197 (1939). 

 " E. D. Warner, J. Exptl. Med., 68, 831-835 (1938). 



9« K. D. Brinkhous and E. D. Warner, Proc. Soe. Exptl. Biol. Med., 44, 609-610 

 (1940). 



99 J. L. BoUman, H. R. Butt, and A. M. Snell, J. Am. Med. Assoc, 115, 1087-1091 

 (1940). 



'»» J. W. Lord, Surgery, 6, 896-898 (1939). 



1" K. IVI. Brinkhous and S. A. Walker, Am. J. Physiol, 132, 666-669 (1941 ). 



