THE COAGULATION OF THE BLOOD 65 



contains no thrombin, since it will not coagulate fluoride- 

 plasma. However, a perfectly cell-free plasma from the bird, 

 or peptone-plasma from the mammal, will clot perfectly with 

 tissue-extract. 



Blood allowed to flow about in the subcutaneous tissues 

 coagulates much more readily than a control sample taken 

 direct from the vessels, 1 and this, together with the observations 

 already described, shows that, though tissue-extracts contain 

 no thrombin, they do contain a substance termed by Morawitz 

 thrombo-kinase, which is concerned in the production of 

 thrombin. 



Although Pekelharing and Delezenne believed that tissue- 

 extract actually exerted its influence in virtue of its fibrin- 

 ferment, Schmidt, Arthus, and Wooldridge denied this, and in 

 a general way the action was attributed to the presence of 

 nucleo-protein. In circulating blood this substance or zymogen 

 is absent, but appears in shed blood. The prothrombin de- 

 scribed by Schmidt he regarded as pre-existent and activated 

 in the presence of lime salts by a zymoplastic substance, shed 

 out of leucocytes. According to Schmidt, this is the substance 

 found in tissue-extract. 



In 1903 Morawitz proved that the zymogen or prothrombin 

 of Schmidt and the zymogen described by Hammersten, Arthus, 

 and Pekelharing are entirely different substances. They are 

 both inactive stages of thrombin. One occurs in oxalate-plasma, 

 and is activated by calcium salts and by nothing else. This 

 is a-prothrombin, and is in part or entirely the material which 

 separates out in cooled oxalate- or peptone-plasma. The other 

 kind of zymogen, that of Schmidt, /3-prothrombin, or Fuld's 

 metazym, is peculiar to the serum separated from coagulated 

 blood. It is non-existent in fluoride-plasma or in oxalate- 

 plasma or in circulating blood. This form is not activated 

 by calcium, but even in the absence of salts of this metal can 

 be activated by weak acids or alkalies. The term metathrombin 

 can be employed for this unactivated stage. 



The development of thrombin from metathrombin is easily 

 produced by weak alkali. When serum is exposed to the air 

 for a few days, any thrombin present completely disappears, 

 and the fluid possesses only metathrombin. In the following 

 table these facts are made clearer : 



1 Arthus, Journ. de Physiologie, iv. p. 281, and Comptes rend. liv. p. 136. 



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