36 THE CIRCULATING LIQUIDS OF THE BODY 



which can be precipitated from them by a stream of carbon dioxide 

 or by sodium chloride. But the addition of a little thrombin 

 causes hydrocele fluid to coagulate. So does the addition of serum, 

 not because of the serum-globulin which it contains, as was once 

 believed, but because of the thrombin in it. The addition of blood- 

 clot, either before or after the corpuscles have been washed away, 

 or of serum-globulin obtained from serum, also causes coagulation 

 of hydrocele fluid, and for a similar reason, the thrombin having a 

 tendency to cling to everything derived from a liquid containing 

 it. On the other hand, serum which, although thrombin is present 

 in it, does not of itself clot, because the fibrinogen has all been 

 changed into fibrin during coagulation of the blood, can be made 

 to coagulate by the addition of hydrocele fluid, which contains 

 fibrinogen. We have thus arrived a step farther in our attempt to ex- 

 plain the coagulation of the blood: it is essentially due to the formation 

 of fibrin from the fibrinogen of the plasma under the influence of 

 thrombin. Up to this point there is agreement between physiologists. 

 Some difference of opinion exists, however, as to the manner in 

 which thrombin is formed or activated when blood is shed, aud a? 

 to the nature of its action upon fibrinogen once it is fully formed. 



The Formation of Thrombin from its Precursors. There is good 

 reason to believe that thrombin is formed by the interaction of three 

 factors: (i) A substance which, since it is a precursor of thrombin, 

 is called thrombogen, or prothrombin. It is already present in the 

 circulating plasma. (2) A substance liberated from the formed ele- 

 ments of the shed blood, but which can be obtained also from the 

 cells of all tissues. Since it has been supposed to act upon throm- 

 bogen, changing it into fully formed thrombin, much in the same 

 way as enterokinase (p. 370) acts upon trypsinogen, changing it 

 into fully formed trypsin, it is called thrombokinase (Morawitz). 

 (3) Calcium ions. The following experiments illustrate the role of 

 these three factors: 



The plasma obtained by drawing off bird's blood e.g., the blood of a 

 fowl or goose through a perfectly clean cannula into a perfectly clean 

 vessel, without contact with the tissues, and then rapidly centrifugal- 

 izing off the formed elements, can be kept unclotted for days and even 

 weeks. The addition of a small amount of tissue extract (procured by 

 rubbing up blood-free liver, thymus, muscle, or other organs with sand, 

 and extracting for several hours with salt solution) to the bird's plasma 

 causes rapid coagulation. The plasma contains thrombogen and 

 calcium salts, but is lacking in thrombokinase, which is supplied by the 

 tissue extract. A solution of fibrinogen containing calcium will clot 

 if serum, in which fibrin -ferment is always present, be added. It will 

 not clot on addition of tissue-extract alone, nor on addition of bird's 

 plasma alone (obtained as above), but will readily coagulate if both 

 tissue extract and bird's plasma be added. Therefore, something in 

 the bird's plasma (thrombogen), plus something in the tissue extract 

 (thrombokinase), produce in the presence of calcium the same effect as 

 the thrombin of serum. It can be shown that calcium is only necessary 



