THE BLOOD 105 



very slowly and gradually, so that there can never in normal cir- 

 cumstances be any massive liberation of fibrin ferment, and, further, 

 that there are agencies at work to neutralise the fibrin ferment as it is 

 formed. The most noteworthy of these neutralising agencies is 

 the presence in the blood of an antiferment called antithrombin, 

 analogous to the antipepsin and antitrypsin which, we have seen, are 

 efficacious in preventing the stomach and intestines from undergoing 

 self-digestion. 



Thrombin or fibrin ferment belongs to the class of nucleo-proteins, 

 and other nucleo-proteins (see pp. 45, 46) obtained from most of the 

 cellular organs of the body produce intravascular clotting when in- 

 jected into the circulation of a living animal. In certain diseased 

 conditions intravascular clotting, or thrombosis, sometimes occurs. 

 This must be due either to the entrance of nucleo-protein into the 

 circulation from diseased tissues, or to a failure of the body to pro- 

 duce sufficient antithrombin to neutralise its effect, or to both of 

 these conditions together. 



Thrombin is believed to originate chiefly from the blood platelets 

 and in part from the leucocytes. Birds' blood clots very slowly, and 

 the absence of blood platelets in this variety of blood will in part 

 account for this. Lymph which contains colourless corpuscles, but 

 no platelets, also clots in time, so in this case the colourless corpuscles 

 must be the source of the ferment. One should, however, be careful 

 in speaking of the disintegration of leucocytes to remember that the 

 word disintegration does not mean complete breakdown, leading to 

 disappearance ; the colourless corpuscles do not appreciably diminish 

 in number when the blood is shed, but what occurs in the surviving 

 leucocytes is a shedding out of certain products, among which fibrin- 

 ferment is one. 



We have now traced fibrin-formation, the essential cause of blood- 

 clotting, to the activity of thrombin ; it is next necessary to allude 

 to what has been discovered in relation to the origin of thrombin. 

 Like other ferments, it is preceded by a mother substance or 

 zymogen. This zymogen is called pro thrombin, or thrombogen, and 

 there appear to be two necessary agents concerned in the con- 

 version of thrombogen into thrombin : one of these is the action 

 of calcium salts, the other is the presence of an activating agent, 

 analogous to entero-kinase (see p. 84), and called thrombo-kinase. 

 The exact role played by each is still a matter of speculation, but 

 we may learn a good deal by studying a little more in detail 

 some of the methods already enumerated for preventing the blood 

 from coagulating. 



