428 VITAMIN K GROUP 



tered clinically in order to reduce the ability of the blood to clot and thus 

 lessen the chances for the development or progression of thromboses. Since 

 the complications of hemorrhage may be as serious as those of thrombosis, 

 the margin of safety is rather narrow. The therapeutic goal is an amount of 

 anticoagulant which will depress prothrombin and associated clotting fac- 

 tors but not quite prolong the whole blood-clotting time. Clinical results 

 have been very encouraging and seem to bear out the empirical method of 

 evaluating therapy.^^ 



Even before the specific toxic agent (dicoumarol) of spoiled sweet clover 

 was known, Roderick^" recognized that the incoagulability of the blood of 

 cattle that had eaten the moldy clover was associated with a prothrombin 

 deficiency. The hypoprothrombinemia requires at least 12 to 24 hours to 

 develop after ingestion of the anticoagulant, probably because an interval 

 of time is required for circulating prothrombin to be catabolized after the 

 production of new prothrombin has been halted. ^^' ^^ This conclusion seems 

 warranted from studies of prothrombin disappearance rates; Carter et al.^^ 

 found no evidence of prothrombin stores. 



Vitamin K concentrates (from alfalfa) or the pure analogs have been 

 found to counteract the prothrombin-depressing activity of dicoumarol. ^^' ^^ 

 The problem remains unsettled as to whether dicoumarol injures the liver, 

 an action reversed by vitamin K or whether there is a competitive inhibi- 

 tion of vitamin K activity by dicoumarol. Glavind and Jansen^^ found that 

 in vitamin K-depleted chicks the reaction to dicoumarol was counteracted 

 by an amount of vitamin K which followed no fixed ratio; they concluded 

 that dicoumarol injures the liver. In a comparable experiment Collentine 



(1944) ; W. D. Battle, R. T. Capps, O. S. Orth, and O. O. Meyer, /. Lab. Clin. Med. 

 35, 8 (1950) ; R. Rotter and O. O. Meyer, ibid. 36, 981 (1950); H. H. Hanson, N. W. 

 Barker, and F. D. Mann, Circulation 4, 844 (1951). 

 " E. V. Allen, N. W. Barker, and J. M. Waugh, J. Am. Med. Assoc. 120, 1009 (1942); 

 H. R. Butt, E. V. Allen, and J. L. Bollman, Proc. Staff Meetings Mayo Clinic 16, 

 388 (1941) ; N. W. Barker, H. R. Butt, E. V. Allen, and J. L. Bollman, J. Am. Med. 

 Assoc. 118, 1003 (1942); N. W. Barker, H. E. Cromer, Jr.,M. Hurn, and J. M. 

 Waugh, Surgery 17, 207 (1945). 



80 L. M. Roderick, Am. J. Physiol. 96, 413 (1931). 



81 K. P. Link, R. S. Overman, W. R. Sullivan, C. F. Huebner, and L. D. Scheel, 

 /. Biol. Chem. 147, 463 (1943). 



82 M. Stefanini and A. V. Pisciotta, Science [N. S.] Ill, 364 (1950). 



83 J. R. Carter, G. H. Chambers, and E. D. Warner, Proc. Soc. Exptl. Biol. Med. 72, 

 52 (1949). 



84 R. S. Overman, J. B. Field, C. A. Baumann, and K. P. Link, J. Nutrition 23, 589 

 (1942). 



85 J. Lehmann, Science [N. S.] 96, 345 (1942); S. Shapiro, M. H. Redish, and H. A. 

 Campbell, Proc. Soc. Exptl. Biol. Med. 52, 12 (1943) ; H. E. Cromer, Jr., and N. W. 

 Barker, Proc. Staff Meetings Mayo Clinic 19, 217 (1944). 



86 J. Glavind and K. F. Jansen, Acta Physiol. Scand. 8, 173 (1944). 



87 G. E. Collentine and A. J. Quick, Am. J. Med. Sci. 222, 7 (1951). 



