FUNCTIONS OF THE BLOOD 283 



of chemical activity, and the destruction of the substance by 

 heating above 60 C. It has been definitely proven that the 

 amount of fibrinogen that is converted to fibrin bears a direct 

 relationship to the amount of thrombin present, and that throm- 

 bin solutions free from protein impurities can be boiled without 

 destroying the thrombin. 



Source of Thrombin. If fresh blood is drawn directly from 

 the veins of an animal into strong alcohol, and the resulting pre- 

 cipitate treated as described above for preparing thrombin from 

 serum, it yields no thrombin; this substance, therefore, which is 

 present in blood-serum, is absent from the blood within the Body 

 and must be formed after the blood is shed and before the forma- 

 tion of the clot. When the process of clotting is watched under 

 the microscope the fibrin threads will usually be seen to form 

 about certain centers. These centers consist of disintegrating 

 blood-plates, and the observation that fibrin formation proceeds 

 from them in this fashion led to the idea that the blood-plates are 

 in some way associated with the process. 



The natural conclusion drawn from this observation was that 

 the blood-plates contain thrombin which is inactive so long as 

 they are intact, and is liberated by their disintegration. This 

 simple conclusion was upset by the further observation that fresh 

 blood drawn into a solution of sodium oxalate will not clot. 

 Sodium oxalate does not hinder the process of blood-plate disin- 

 tegration. In fact its sole effect upon blood, so far as can be de- 

 termined, is to precipitate out its calcium, as calcium oxalate. 

 That the prevention of clotting is due to this precipitation of cal- 

 cium is shown by the fact that addition of excess of a soluble cal- 

 cium salt to " oxalate " blood causes it to clot with great prompt- 

 ness. The formation of active thrombin is dependent, then, upon 

 the presence of calcium in the blood, and the substance contained 

 in the blood-plates is not true thrombin, but a preparatory sub- 

 stance which we may call prothrombin. 



Summary of the Process of Coagulation. We may picture the 

 entire process of blood-clotting somewhat as follows: 



1. As the result of exposure to a foreign environment the blood- 

 plates disintegrate, yielding prothrombin. 



2. The prothrombin thus set free reacts with the calcium of the 

 blood and forms thrombin. 



