COAGULATION. 459 



We owe to Arthus and Pages, however, the proof that calcium 

 salts are essential to the process of normal coagulation. These 

 observers showed that freshly drawn blood allowed to flow into 

 an oxalate solution, in amounts such that the final concentration 

 in oxalate is not less than 0.1 per cent., will remain unclotted in- 

 definitely, but may be made to clot at any time by the addition 

 of a suitable amount of calcium salt. That this effect is not due 

 to an excess of the added oxalate is proved by the fact that the 

 oxalated blood or the plasma obtained from it by centrifugali- 

 zation may be dialyzed against a large bulk of solution of sodium 

 chlorid, 0.9 per cent., until the excess of oxalate is removed. 

 This dialyzed plasma will remain unclotted indefinitely, but 

 coagulates promptly upon the addition of small amounts of cal- 

 cium chlorid. It has been shown quite conclusively by Ham- 

 marsten that the calcium is not directly concerned in the con- 

 version of the fibrinogen to fibrin; the thrombin is able to effect 

 this change in the absence of calcium. The dialyzed oxalated 

 plasma spoken of above is readily clotted if some thrombin solu- 

 tion free from calcium salts is added to it. The role of the calcium 

 lies in the part that it takes in the conversion of the prothrombin 

 to thrombin. According to the terminology used at present, we 

 may say that calcium is necessary for the activation of the throm- 

 bin. In the oxalated plasma fibrinogen and prothrombin or inac- 

 tive thrombin are present, and the addition of calcium salts serves 

 simply to convert the prothrombin to thrombin. We may be- 

 lieve that this reaction occurs always in the initial stages of normal 

 clotting. 



Influence of Tissue Extracts Upon Coagulation. Another im- 

 portant consideration in the normal clotting of blood is the in- 

 fluence of extracts of tissues upon the rapidity of the process. 

 Many observers have shown that certain substances are contained 

 in the tissues in general, including the blood-corpuscles, which 

 tend to accelerate the process of clotting. Arthus, for example, 

 found that blood taken directly from the artery of a mammal 

 through a clean tube will clot within a certain time, while if allowed 

 to flow first over the wounded surface, as happens under normal 

 conditions, the time of clotting is much accelerated. This in- 

 fluence of the tissues is shown in an extreme way when we consider 

 the blood of the lower vertebrates, the birds, reptiles, and fishes. 

 If blood is drawn from an artery of one of these animals through 

 a clean tube it clots with great slowness. If such a specimen of 

 blood is centrifugalized promptly the supernatant plasma, when 

 pipetted off, may remain unclotted for many hours or fail to clot 

 at all. If, however, the drawn blood or the centrifugalized plasma 

 is mixed with an extract from the animal's tissues, the muscles, 



