654 PHYSIOLOGICAL CHEMISTRY. 



ceived into a cold, narrow glass cylinder, and allowed to stand at 

 C., the blood may be kept fluid for several days. The corpuscles 

 will deposit in a red layer from the plasma. 



It may readily be shown that the clotting of blood is due to a 

 change of some kind which converts the soluble protein fibrinogen 

 into an insoluble form called fibrin. Fibrinogen is one of the globu- 

 lins, it coagulates at a temperature of from 50 to 60 C., and is pre- 

 cipitated by half- saturation with sodium chloride. It is present also 

 in lymph. 



It is well known that the clotting of fibrinogen is produced by an 

 organic substance formerly called fibrin-ferment, but preferably called 

 thrombin, as it is probably not an enzyme. It is also known that this 

 thrombin is active only in the presence of calcium salts ; that is, that 

 inactive thrombin (prothrombin or thrombogen) is changed by cal- 

 cium into the active form. It is, however, possible to remove the 

 calcium from activated thrombin without impairing its activity ; 

 therefore the calcium does not enter directly into the conversion of 

 fibrinogen into fibrin. 



As calcium is present in all blood, it is evident that in cir- 

 culating blood either prothrombin must not be present as such, 

 or, if present, its activation by the calcium must be prevented by 

 some antagonistic substance (antithrombin), for otherwise clotting 

 would occur within the blood-vessels, which does not happen under 

 normal conditions. Accordingly, there are two theories to explain 

 these facts. 



Morawitz believes that in order to convert prothrombin into throm- 

 bin, not only calcium but also a secondary organic substance (throin- 

 bokinase) must be present, and that this thrombokinase is furnished 

 to blood which has escaped from the blood-vessels by the injured 

 leucocytes and platelets. The other view, to which Howell inclines, 

 is that prothrombin is transformed into thrombin by calcium salts 

 alone, and that this change is prevented by the antithrombin of 

 the circulating blood, and that when the blood is shed the injured 

 cells set free a zymoplastic substance which counteracts the anti- 

 thormbin and leaves the calcium free to convert the prothrombin 

 into thrombin. 



The different methods of preventing the clotting of blood 

 are to be explained thus : The cooling of blood probably pre- 

 vents the formation of the thrombokinase, or the thromboplas- 

 tic substances, by preserving the cells intact. The addition of 



