VII. EFFECTS OF DEFICIENCY 433 



with biliary fistulas, Hawkins and Brinkhous'"' detected severe hypopro- 

 thrombinemia. In these various hemorrhagic states, all attributable to a 

 deficiency of vitamin K, and studied by a variety of methods, the common 

 denominator has been found to be a lack of the plasmatic precursor of 

 thrombin. When this clotting change was found to be readily corrected by 

 vitamin K it was felt"^^ — and is still generally believed — that the lack of 

 prothrombin is the only immediate result of vitamin K deficiency, and hence 

 the sole cause of bleeding in this deficiency state. 



Such a simple, attractive concept — pure hypoprothrombinemia — over- 

 looks some disturbing facts. The newborn infant has a prothrombin value 

 only one-fourth to one-third that of adults.^"* The prothrombin titer rises 

 slowly, reaching normal adult levels near the end of the first year of life. 

 Despite this rather pronounced hypoprothrombinemia, the newborn's clot 

 time is normal or even shortened, and the "prothrombin time" of Quick is 

 usually normal; bleeding rarely occurs under these circumstances.*- ^^•^^' 

 114, 115 During the first week of life drastic changes occur; generally between 

 the second and fifth days the "prothrombin time" is prolonged and clot 

 times may be lengthened; if these changes are extreme, hemorrhage may 

 ensue — clinically described as "hemorrhagic disease of the newborn." Actual 

 bleeding is uncommon, and spontaneous return to normal takes place by 

 the end of the first week of life, if digestive disturbances have not inter- 

 vened."^ It is well known that vitamin K and its analogs can prevent or 

 quickly correct these clotting and bleeding changes. Yet, throughout this 

 brief neonatal period the true prothrombin level of the blood is low and 

 fluctuates little. 



Here, then, is one instance of hemorrhagic diathesis developing without 

 a significant alteration in the plasma prothrombin concentration, and what- 

 ever the abnormality may be, vitamin K is corrective. 



Mann and Hurn"^ have described a new blood coagulation factor whose 

 activity appears to be related to the function of thromboplastin in the first 

 stage of clotting, hence "cothromboplastin." When this factor is deficient, 

 prothrombin, regardless of how much is present, can convert to thrombin 

 only with difficulty; as a result of a deficiency of cothromboplastin the 

 "prothrombin time" of Quick is prolonged. It has been found that cothrom- 



"3 Reviewed by K. M. Brinkhous, Medicine 19, 329 (1940). 



114 w. W. Waddell, Jr., and D. Guerrj-, III, /. Am. Med. Assoc. 112, 2259 (1939). 



"5 C. A. Owen, G. R. Hoffman, S. E. Ziffren, and H. P. Smith, Proc. Soc. Exptl. Biol. 



Med. 41, 181 (1939); H. Dam, E. Tage-Hansen, and P. Plum, Lancet II, 1157 (1939); 



E. Oehler, Monatsschr. Kinderheilk. 90, 394 (1942). 

 '16 F. Widenbauer and U. Krebs, Monatsschr. Kinderheilk. 90, 173 (1942); S. Rapoport 



and K. Dodd, Am. J. Diseases Children 71, 611 (1946). 

 "7 F. D. Mann, Am. J. Clin. Pathol. 19, 861 (1949); F. D. Mann and M. M. Hurn, 



ibid. 20, 225 (1950). 



