320 DISTURBANCES OF CIRCULATION . 



substance which increases coagulation and also another substance 

 retarding coagulation; the first of these is destroyed by the liver, leaving 

 the retarding substance to act unopposed.^* Leech extract (hirudin) 

 prevents clotting by means of an antiferment action, combining with 

 the thrombin. ^^ Snake venom, however, acts upon the thrombokinase 

 (Morawitz). 



Coagulability of the Blood in Disease. — In disease the altera- 

 tions in the coagulability of the blood depend upon much the same 

 factors. In all conditions associated with suppuration and leucocyto- 

 sis the amount of fibrinogen is increased. This is especially true of 

 pneumonia.^° The fluidity of the blood in septicemia is probably 

 dependent upon the appearance of the coagulation-inhibiting phase 

 that follows the action of the products of cell destruction, including 

 among them proteoses. In this connection should be mentioned the 

 observation of Conradi,^^ who found that among the products of au- 

 tolysis is a coagulation-inhibiting substance which is not destroyed by 

 heat, diffuses readily, and in general behaves unlike the proteins. This 

 or similar substances may well play a part in affecting coagulation in 

 infectious diseases, and Whipple^^ has found a decreased coagula- 

 bility in septicemia because of the presence of an excess of anti- 

 thrombin. It may also be mentioned that animals soon acquire an 

 immunity against proteoses, so that their inhibiting influence is no 

 longer shown. This corresponds to the observation of Kanthack^^ 

 that immune serum against venom neutralizes very effectively the 

 anticoagulating principle of venom; an amount of antiserum alto- 

 gether insufficient to neutralize the toxic properties of venom will 

 neutralize its property of preventing clotting. The bacterial prod- 

 ucts may also modify coagulation, and L. Loeb^"* has found that 

 different organisms are unequally effective in this respect, Staphylo- 

 coccus aureus being much more powerful in causing coagulation than 

 any others tested ;^^ typhoid, diphtheria, tubercle, and xerosis bacilli 

 and streptococci being without any apparent effect, while pyocyan- 

 eus, prodigiosus, and colon bacilli occupy an intermediate position. 

 Furthermore, after the organisms are killed bj- boiling, this effect is 

 greatly reduced, showing that it does not depend merely upon the 

 mechanical action of the bacteria, but probabi}' upon bacterial prod- 

 ucts contained in the culture-media. 



^* Tlic manner in which gelatin injections afl'ect the blooil coagulability is not 

 yet understood (see Hoggs, Deut. Arch. klin. Med.. 1<)04 (79), 539); Moll (Wien. 

 klin. Woch., 1903 (16), 1215) found an increase in fibrinogen. 



" Hirudin may contain antikinase (Mellanbv, Jour, of I'hvsiol., 1909 (38), 441). 



8" Dochez, Jour. Exp. Med., 1912 (10), 093. 



" Hofmeister's Beitr., 1901 (1), 137. 



s'' Arch. Int. Med., 1912 (9), 305. 



'* Cited 1)V Lazarus-Barlow, p. 141. 



«< Jour. Aicd. Research, 1903 (10), 407. 



*^ Much (Biochem. Zeit., 1908 (14), 143) states that staphylococcus contains 

 thrombokinase. 



