COAGULATIOS OF THE ULOOD 319 



agulation whieli may, particularly in the ease of org'au extracts, 

 cause prompt death from intravascular clotting; if the animal sur- 

 vives, there follows a period of decrease or total iiihil)ition of co- 

 agulability of the blood, both within the vessels and after removal 

 from the body. The first period of increased coagulability undoubt- 

 edly depends upon the formation of a large amount of fibrin-ferment, 

 but it has not yet been satisfactorily explained how the inhibition of 

 coagulation is i)r()duced. Apparently the fibrin-ferment formed at 

 first is rai)idly destroyed, but it is thought by some that it is con- 

 verted into a substance that neutralizes the fibrin-ferment that may 

 be formed later, or that a true anticoagulin is formed. It is also 

 among the possibilities that all the available prothrombin or throm- 

 bokinase is used up during the first stage of acceleration. As before 

 ]nentioned, the blood and tissues contain substances that inhibit 

 coagulation, and it may be that these are secreted in excessive 

 amounts, a view which is receiving much support from recent observa- 

 tions. According to Davis "'- injection of tlirombin is followed quickly 

 by an increase in the amount of antithrombin in the blood. It has 

 been found that in animals deprived of the liver no coagulation- 

 inhibiting substances are formed in the blood after injection of pro- 

 teoses, hence Delezenne believes that the substances of this class act 

 by causing a destruction of leucoc3'tes, thus liberating a substance 

 which increases coagulation and also another substance retarding co- 

 agulation ; the first of these is destroyed by the liver, leaving the re- 

 tarding substance to act unopposed."' Leech extract {hirudin) pre- 

 vents 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 alterations 

 in the coagulability of the blood depend upon much the same factors. 

 In all conditions associated with suppuration and leucocytosis the 

 amount of fibrinogen is increased. This is especially true of pneu- 

 monia.^^ The fluidity of the blood in septicemia is probably dependent 

 upon the appearance of the coagulation-inhibiting pha.se 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 autolysis is a 

 coagulation-inhibiting substance which is not destroyed by heat, dif- 

 fuses readily, and in general behaves unlike the proteins. This or 



32Amer. Jour. Physiol., 1011 (29), 160. 



33 The manner in whieh gelatin injections affect tlie blood coaffulability is not 

 yet understood (see Boggs, Deut. Arcli. klin. :\Ied., 1004 (70), 530) ; Moll (Wien. 

 klin. Woch., 1003 (16), 1215) found an increase in fibrinogen. 



3* Hirudin mav contain antikinase (Mellanby, Jour, of Phvsiol.. 1000 (38), 

 441). 



35Dochez, Jour. Exp. Med., 1012 (16), 603. 



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



