COAGULATION 41 



But it will always activate the thrombogen of an animal of the 

 same kind. 



To sum up, we may say that when blood is shed, thrombin is rapidly 

 formed by the action of thrombokinase, liberated from the leucocytes, 

 the blood-plates, and possibly to some extent from the erythrocytes, 

 upon thrombogen, already present in the circulating plasma. Further 

 and this is of great practical importance since no vessel is opened 

 under ordinary circumstances except through a wound in the overly- 

 ing structures, the cut tissues supply a store of thrombokinase at 

 the point where it is required to aid in the stanching of the wound. 

 Calcium is essential to the reaction by which thrombogen and thrombo- 

 kinase form thrombin, but is not necessary for that action of thrombin 

 on fibrinoges by which fibrin is produced (Practical Exercises, 

 pp. 62-65). 



The Nature of the Action of Thrombin on Fibrinogen. The usual 

 view, first advanced by Schmidt many years ago, is that thrombin 

 acts as an enzyme. Hence it is often spoken of as fibrin-ferment. 

 In support of this theory it has been stated that the thrombin 

 does not itself seem to be used up in the process, nor to enter bodily 

 into the fibrin formed; that a small quantity of it can cause an 

 indefinitely large amount of fibrinogen to clot; and that its power 

 is abolished by boiling (p. 331). There has been a disposition 

 among more recent observers to question this evidence. Accord- 

 ing to Rettger, the quantity of fibrin formed when a small amount of 

 thrombin is added to a fibrinogen solution tends to a fixed maxi- 

 mum, which does not increase with the time of action.* Under 

 certain conditions, also, it is said that thrombin is not destroyed at 

 the temperature of boiling water. Whatever the precise nature of 

 the reaction which leads to the precipitation of the fibrinogen in the 

 form of fibrils, thrombin is very loosely combined if combined at 

 all in the fibrin, since it is readily extracted by an 8 per cent, 

 solution of sodium chloride. This, indeed, is one of the best ways 

 of obtaining an active thrombin solution. 



The view which we have followed above, in accordance with 

 Morawitz, that the substances in tissue extracts which favour 

 coagulation do so by activating prothrombin to fully formed 

 thrombin, has also been opposed by a number of the more recent 

 workers. Some consider that they exert a direct action upon 

 fibrinogen similar to, although not necessarily identical with, that 

 of thrombin, and speak of them as coagulins (L. Loeb). Howell 

 holds that these substances, which he prefers to term thromboplastic 

 substances, since this makes no assumption as to their mode of 

 action, play a quite different role, namely, that of neutralizing anti- 

 thrombin. His observations have led him to the conclusion that 



* The inquiry is complicated by the fact that fibrin, once formed, tends to 

 adsorb the remaining thrombin and so to interfere with its further action. 



