450 THE BLOOD [CH. XXIX. 



does not ionise in solution so as to liberate the free calcium ions 

 which are essential for thrombin formation. 



Oxalated blood (or oxalated plasma) will clot when the calcium 

 is once more restored by the addition of a small amount of calcium 

 chloride, but such addition to fluoride plasma will not induce clotting ; 

 in this case, thrombin itself must be added as well. In some way 

 sodium fluoride interferes with the formation of thrombin, probably 

 by preventing the liberation of thrombokinase from the corpuscular 

 elements of the blood. The latter are certainly very well preserved. 



The second activating agent, however, thrombokinase, is not only 

 liberated from the blood-corpuscles, but it is also obtained from many 

 other tissues. If a haemorrhage takes place under ordinary circum- 

 stances the blood as it flows from the wound passes over the muscles 

 and skin that have been cut, and rapidly clots owing to the throm- 

 bokinase supplied by those tissues. If blood is obtained by drawing 

 it off through a perfectly clean cannula into a clean vessel without 

 allowing it to touch the tissues, it remains unclotted for a long 

 time ; in the case of birds' blood this time may extend to many days ; 

 but the addition of a small piece of a tissue such as muscle, or of an 

 extract of such a tissue, produces almost immediate clotting. If a 

 solution of fibrinogen is prepared and calcium added it will not clot ; 

 if thrombin, or a fluid such as serum which contains thrombin, is added 

 it will clot. It will not clot if birds' plasma obtained as above is added 

 to it ; nor if tissue extract is added to it ; but if both are added it will. 

 In other words, the thrombogen of the birds' plasma plus the throm- 

 bokinase of the tissue extract have the same effect as thrombin. 



The next point to consider is why blood obtained after the 

 previous injection of proteoses (or commercial peptone) into the 

 circulation does not clot. It certainly contains calcium salts, and 

 probably both thrombogen and thrombokinase, for it can be made to 

 clot without the addition of either, for instance by dilution, or the 

 passage of a stream of carbon dioxide through it. There must be 

 something in peptone blood which antagonises the action of thrombin. 

 This something is an excess of . an ti thrombin. Peptone will not 

 hinder blood : coagulation, or only very slightly, if it is added to the 

 blood after it is shed. The antithrombin must therefore have been 

 added to the blood while it was circulating in the body. We can 

 oven go further than this, and say what part of the body it is which 

 is concerned in the production of antithrombin. It is the liver ; for 

 if the liver is shut off from the circulation, peptone is ineffective in 

 its action. The converse experiment confirms this conclusion, for if 

 a solution of peptone is artificially perfused through an excised 

 surviving liver, a substance is formed which has the power of hinder- 

 ing or preventing the coagulation of shed blood. Peptone blood is 

 very poor in leucocytes; the cause of their disappearance is not clear. 



