418 BLOOD AND LYMPH. 



but when a calcium-free solution of fibrinogen is brought into reac- 

 tion with a calcium-free ferment solution (blood-serum) a typical 

 clot is formed the fibrin of which is practically free from calcium. 

 This result also enables us to draw the important conclusion that 

 the calcium is not essential to the process of clotting after the 

 thrombin is once formed, and that therefore its role probably comes 

 in in the production of the thrombin. 



Practically all recent observers hold to the view that the 

 active thrombin is formed from an inactive antecedent substance 

 which is designated usually as prothrombin. Schmidt and others 

 believe that the prothrombin exists preformed in blood-plasma and 

 that it may be converted into active thrombin by certain substances 

 arising from the blood corpuscles or indeed from many tissue cells. 

 These substances are described as zymoplastic substances (also 

 cytozyms or coagulins). Others have considered that the calcium 

 salts constitute the efficient zymoplastic substance that converts 

 the prothrombin to thrombin, a view that is contained in the first 

 part of Pekelharing's theory, given above. At present it would 

 seem necessary to adopt a combination of these views: to suppose 

 that in the formation of active thrombin three factors co-operate, 

 namely, the calcium salts, the prothrombin, and zymoplastic sub- 

 stances. The calcium salts exist in solution in the plasma, the 

 prothrombin also according to some authors pre-exists in the plasma, 

 while according to others it is furnished by the cellular elements 

 (blood plates, leucocytes). The zymoplastic substance is a ferment 

 body derived from cellular elements; it has been designated by 

 several names, such as cytozym (Fuld), to indicate its origin from 

 cells, and thrombokinase (Morawitz),to indicate its activating effect 

 upon the prothrombin. The latter name seems preferable, and it 

 is important to bear in mind that such bodies may be furnished 

 not only by the formed elements of the blood, but also by other 

 tissue elements. Thus, Delezenne has shown that if the blood of 

 birds is withdrawn carefully, by means of a cannula inserted into 

 an artery, it clots very slowly, and if centrifugalized at once the 

 supernatant plasma when removed may remain unclotted for some 

 days. This result seems evidently to be due to the fact that the 

 elements in the blood of these animals supposed to correspond with 

 the blood plates of mammalia disintegrate much less readily. A 

 similar result holds good for the blood of terrapins, as was pointed 

 out long ago by the present author. If, however, in withdrawing 

 the blood it comes into contact with the tissues, at the wound, 

 for instance, it will clot quickly, and it would appear that a 

 zymoplastic substance is furnished by the tissues. In the bird 

 the normal clotting of the blood to stop wounded vessels must de- 

 pend evidently upon this co-operation from the outside tissues. In 



