INTERNAL SECRETION AND DISORDERS OF LIVER 681 



amount of antithrombin in the blood. In hemophilia the antithrombin 

 may be normal or somewhat increased. In spontaneous thrombosis of the 

 veins the antithrombin is diminished, and in purpura hemcrrhagica, and 

 in other forms of so-called purpura, no evidence was found of any varia- 

 tion from the normal. Drinker and Drinker (1915) found that rapid 

 progressive hemorrhage in animals causes a progressive shortening of the 

 coagulation time, and a parallel or greater diminution in antithrombin, 

 Minot, Denny and Davis (1916), using Howell's method, have also stud- 

 ied quantitatively the antithrombin in various pathological conditions in 

 man. A positive increase in antithrombin content of the blood is indicated 

 in three cases only, namely, acute splenomyelogenous leukemia, aleukemic 

 leukemia and congenital hemophilia. Diminution in antithrombin was 

 found especially in cases of severe typhoid fever, certain leukemias, ane- 

 mias and thrombosis. 



The majority of authors agree that antithrombin plays the important 

 role of protecting the blood from clotting within the vessels. Before 

 drawing a definite conclusion that antithrombin, as such, is an internal 

 secretion of the liver one should review briefly the recent work on blood 

 coagulation. A survey of the results indicates that at least eight different 

 substances are concerned in one way or another in the process ; namely, 

 fibrinogen, thrombin, heparin, prothrombin, calcium, pro-antithrombin, 

 antithrombin, and the so-called zymoplastic or thromboplastic substances 

 (cephalin) furnished by the tissue cells in general, including the blood 

 corpuscles. 



Pro-Antithrombin and Heparin as Hepatic 

 Internal Secretions 



These two substances have been described by Howell (b) (1916-17) 

 and by Howell and Holt (1918). They designate pro-antithrombin as the 

 antecedent or mother substance, present in blood plasma or blood serum, 

 from which antithrombin is formed by a reaction with heparin. By a 

 reaction analogous to the activation of prothrombin to thrcmbin by cal- 

 cium, the pro-antithrombin is activated to antithrombin by heparin. Hepa- 

 rin is described as a phosphatid which exists in various tissues, but is 

 found most abundantly in the liver. It possesses two characteristic re- 

 actions. First, it retards or prevents the coagulation of the blood, both in 

 the body and when the blood is shed, mainly by preventing the activation 

 of prothrombin to thrombin. In this respect it acts as an antiprothrombin 

 rather than as an antithrombin. Second, it causes a marked increase in 

 antithrombin when added to blood or serum by activating the pro-anti- 

 thrombin to antithrombin. 



On the theoretical side, Howell and Holt suggest that heparin and pro- 



