CH. XXIX.] COAGULATION OF THE BLOOD 449 



occurs in the heart and main blood-vessels, is fatal. The condition 

 is doubtless due to the entrance of nucleo-protein into the circula- 

 tion from disintegrated cells. The relationship of nucleo-protein 

 and thrombin is an unsettled problem ; the old view that the two 

 are identical is probably incorrect ; it is, however, possible that the 

 nucleo-protein is either identical with thrombokinase, or holds the 

 thrombokinase in loose combination or admixture. 



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 cor- 

 puscles, but no platelets, also clots, 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 clots, but what 

 occurs is a shedding out from the surviving leucocytes 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 enzymes, 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 

 conversion of thrombogen into thrombin ; one of these is the action 

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

 (analogous to the enterokinase, which activates pancreatic juice) 

 called thrombokinase. 



The part played by calcium salts is well illustrated by the fact 

 that coagulation is prevented by the decalcification of the blood. 

 This can be accomplished by the addition of a small amount of a 

 soluble oxalate or fluoride to the blood immediately it is shed. The 

 calcium of the blood plasma is then immediately precipitated as 

 insoluble calcium oxalate or fluoride, and is thus not available for 

 the transformation of thrombogen into thrombin. The addition of the 

 oxalate or fluoride must be rapidly performed, otherwise time will be 

 given for the conversion of thrombogen into thrombin, and thrombin, 

 when formed, will act upon fibrinogen whether the calcium has been 

 removed or not. In other words, calcium is only necessary for the 

 formation of fibrin-ferment, and not for the action of fibrin-ferment 

 on fibrinogen. Fibrin is thus not a compound of calcium and 

 fibrinogen. 



The action of a soluble citrate is also, in a certain sense, a 

 decalcifying action, for although calcium citrate is a soluble salt, it 



2 F 



