432 VITAMIN K GROUP 



phenylindanedione is relatively brief because this substance reduces glomer- 

 ular capillary resistance and is excreted rapidly; to counteract this phe- 

 nomenon, vitamin P has been used to increase the capillary resistance, 

 apparently successfully. 



Link's group^**^ has synthesized dicoumarol from and degraded it to 

 salicylic acid. Since salicylates have a limited anticoagulant action, it has 

 been suggested that dicoumarol may act through its degradation prod- 

 ucts.^^' ^''^' ^"^ The relative inefficiency of salicylates (1/500 the activity of 

 dicoumarol) makes this unlikely; however, one might speculate with Jaques 

 and Lepp^"^ that intestinal bacteria convert a small portion of ingested 

 salicylate into dicoumarol. Arguing along similar lines, Shemiakin and 

 coworkers^ '^^ believe that phthalates are biologic degradation products of 

 vitamin K and are responsible for the naphthoquinone 's coagulant activity. 



For the effect of other drugs on blood clotting the excellent review of 

 Seegers^"^* is referred to. 



3, Blood Coagulation Changes with Vitamin K Deficiency 



Hemorrhage associated with obstructive jaundice has been known and 

 reported for centuries; vascular changes, deficiency of various clotting com- 

 ponents, and the presence of clot-inhibiting agents have all been suggested. 

 Of the older concepts only the suggestion that antithrombin is excessive in 

 vitamin K deficiency persists. Dyckerhoff and Marx^°^ claim that the 

 increased thrombin-destroying function of plasma is corrected by adminis- 

 tration of the vitamin. 



Quick et al.,^^ in 1935, announced that prothrombin was lacking in the 

 poorly coagulable blood of a patient with obstructive jaundice. In the 

 hemorrhagic chick disease of dietary origin Sch0nheyder"*^ suspected a 

 deficiency of plasma prothrombin; Dam et al}^^ clearly demonstrated that 

 adding prothrombin from normal plasma corrected this deficiency; further, 

 they were unable to recover prothrombin, by acetone or isoelectric precipita- 

 tion, from the plasma of bleeding chicks. Quick"^ convincingly confirmed 

 the prothrombin lack in the chick bleeding state. In the bleeding of dogs 



«4 M. A. Stahmann, C. F. Huebner, and K. P. Link, J. Biol. Chem. 138, 513 (1941). 



»5 S. Shapiro, /. Am. Med. Assoc. 125, 546 (1944). 



06 O. O. Meyer and B. Howard, Proc. Soc. Exptl. Biol. Med. 53, 234 (1943); S. Rapo- 



port, M. Wing, and G. M. Guest, ibid. 53, 40 (1943). 

 »7 L. B. Jaques and E. Lepp, Proc. Soc. Exptl. Biol. Med. 66, 178 (1947). 



08 M. M. Shemiakin, L. A. Schukina, and J. B. Shevezov, Nature 151, 585 (1943) ; M. 

 M. Shemiakin and L. A. Schukina, ibid. 154, 513 (1944). 



08a W. H. Seegers, Pharmacol. Revs. 3, 278 (1951). 



09 H. Dyckerhoff and R. Marx, Biochem. Z. 311, 1 (1942). 



10 F. Sch0nheyder, Biochem. J. 30, Part 1, 890 (1936). 



11 H. Dam, F. Sch0nheyder, and E. Tage-Hansen, Biochem. J. 30, Part 1, 1075 (1936). 



12 A. J. Quick, Am. J. Physiol. 118, 260 (1937). 



