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,! 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, @-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. 
5 
