460 BLOOD AND LYMPH. 



servers have called attention to the fact that calcium salts in cer- 

 tain concentrations influence favorably the coagulation of blood. 

 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. Much discussion has ensued 

 in regard to the precise role played by calcium in the process of 

 clotting. The outcome of this work justifies the statement that 

 calcium is not concerned in the final stage of clotting; namely, the 

 reaction between fibrinogen and thrombin, but takes an essential 

 part in the first stage, the conversion of prothrombin to thrombin. 

 According to the terminology used at present, we may say that 

 calcium is necessary for the activation of the thrombin. In the 

 oxalated plasma fibrinogen and prothrombin or inactive thrombin 

 are present, and the addition of calcium salts serves simply to con- 

 vert the prothrombin to thrombin. If fully formed thrombin 

 prepared by any of the methods described is added to oxalated 

 plasma clotting occurs, although no calcium is present. 



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 animaPs tissues, the muscles, 

 for example, it will clot within a few minutes. This is, of course, 

 what happens in such animals when wounded. The escaping 

 blood oozes over the cut surface and clotting occurs promptly. 

 Mammalian blood differs from that of the lower vertebrates in 

 that it clots within a relatively short time, even if kept from coming 

 in contact with the injured tissues, and this difference may be ex- 



