460 BLOOD AND LYMPH. 



are three colloids, fibrinogen and thrombogen furnished by the liver and 

 thrombozym derived from the leucocytes. These colloids unite to form fibrin, 

 but in order for the reaction to take place calcium must be present, as also 

 thromboplastic substance. Bordet and Delange* explain the formation of 

 thrombin as due to a reactioii between substances designated as cytozym and 

 serozym. The cytozym is furnished by the platelets (and tissues). It is not 

 destroyed by boiling. The serozym is a substance not present in blood, but 

 formed in some way after the blood is shed. It is destroyed by heating to 

 55° C. The reaction between cytozym and serozym requires the presence of 

 calcium salts. 



Why Blood Does Not Clot Within the Blood-vessels.— The 



specific explanation of the fluidity of the blood within the vessels 

 must vary, of course, with the theory of coagulation that is adopted. 

 In general, it may be stated with confidence that the circulating 

 blood contains no active thrombin, or at least not enough to clot 

 the blood, and the real difficulty we have to explain is how the 

 prothrombin is kept in an inactive state throughout life. Ac- 

 cording to Morawitz, everything turns on the fact that tlii-ombo- 

 kinase is absent. The fibrinogen, prothrombin, and calcium are 

 in solution in the blood-plasma, but according to his theory the 

 kinase is essential to aid the calcium in activating the prothrombin. 

 Cellular elements, platelets, leucocytes, erythrocytes doubtless are 

 constantly undergoing disintegration in the circulation and thereby 

 furnish some kinase, but under normal conditions this does not 

 occur in mass, as is the case in shed blood. The explanation is 

 logically satisfactory, if we accept the theory of a kinase, although 

 it does not accord very well with the fact that large amounts of 

 tissue extracts, containing the kinase, may be injected into the 

 circulation without producing intravascular clotting. Another 

 point of view is that the normal fluidity of the blood is maintained 

 by the constant presence of an inhibiting substance. Two sub- 

 stances of this kind are known. One of them, designated in gen- 

 eral as antithrombin, has the property of preventing the reaction 

 between thrombin and fibrinogen. As a definite example of an 

 antithrombin we have the protein material secreted by the salivary 

 gland of the leech (Hirudo medicinahs) and known as Hirudin. 

 This material may be extracted in relatively pure form from the 

 head of the leech. It can be obtained commercially and is used 

 frequently in laboratory experiments to prevent the clotting of 

 blood. A similar substance is present in very small concentrations 

 in the mammalian blood and in larger amounts in the blood of the 

 lower vertebrates. Whether or not this antithrombin of the blood 

 is identical with the hirudin of the leech is not known, but its 

 action is similar, that is to say, it retards or prevents the reaction 

 between thrombin and fibrinogen. As to its function in the blood, 



* "Annales de I'institut Pasteur," 26, 657 and 737, 1912. 



