COAGULATION. 463 



initiated by the production of a new substance, the thromboplastic 

 substance, furnished by the cells or blood-corpuscles (plates), 

 but on one view this substance acts as a kinase which participates 

 directly in the conversion of prothrombin to thrombin, while on 

 the other view the substance permits this conversion to occur 

 indirectly by neutralizing the opposing antithrombin. 



Several other theories of coagulation are proposed, but they are difficult 

 to explain in a few words. Two of the most recent of these theories may be 

 referred to briefly. According to Nolf* the essential factors of coagulation 

 are three colloids, fibrinogen an/i 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 Delangef explain the formation of 

 thrombin as due to a reaction 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. Anti- 

 thrombin. The specific explanation of the fluidity of the blood 

 within the vessels must vary, of course, with the theory of coagula- 

 tion 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 ex- 

 plain is how the prothrombin is kept in an inactive state through- 

 out life. According to Morawitz, everything turns on the fact 

 that thrombokinase 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, erythro- 

 cytes 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 intravascu'ar 

 clotting. Another point of view is that the normal fluidity of the 

 blood is maintained by the constant presence of an inhibiting sub- 

 stance. Substances of this kind are known. The one that is most 

 familiar is hirudin, a protein body prepared from the salivary gland 

 of the leech (Hirudo medicinalis). Hirudin is readily soluble in 

 water and has the property of preventing the action of thrombin 

 upon fibrinogen. It may be designated properly, therefore, as an 

 antithrombin. It is much used in experimental work when it is 



* "Archives internationales de physiol.," 6, 115, 1908. 

 t "Annales de Tinstitut Pasteur,"~26, 657 and 737, 1912. 



