DISEASE-RESISTING FUNCTIONS OF THE BLOOD 317 



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. So- 

 dium 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 

 calcium salt to " oxalate" blood causes it to clot with great 

 promptness. 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 prepara- 

 tory substance which we may call prothrombin. 



Antithrombin. A feature of the coagulation process that pre- 

 sents some difficulty is that although the circulating blood contains 

 all the essential factors of the process, clotting does not occur in it 

 so long as it circulates normally, but only when it escapes from the 

 vessels or when the lining of these is injured. To say that the 

 prothrombin is stored in the platelets and so kept from combining 

 with calcium to form thrombin seems an insufficient protection 

 against the possible accident of a decomposition of platelets in the 

 blood-stream. 



Definite evidence has been obtained of the existence of a sub- 

 stance which will prevent clotting. This substance is present in 

 the salivary glands of leeches, and serves to keep the blood which 

 they ingest liquid in their stomachs. To it has been given the 

 name antithrombin. Snake venom contains similar material. 

 What is believed to be the same substance is produced within the 

 bodies of some animals (dogs) by injecting unpurified peptone 

 solutions into their veins. There is reason to believe that normal 

 blood contains antithrombin in sufficient amounts to prevent 

 clotting within the blood-vessels. If this substance is present in 

 the blood it must be neutralized when the blood is shed to allow 

 coagulation to proceed. 



Thromboplastic substance. An observation that throws light 

 on the manner in which antithrombin is neutralized when blood 

 is shed is that if the blood is drawn from a vessel directly into a 



