COAGULATION. 461 



plained on the view that the accelerating substance furnished 

 by the tissues in the lower vertebrates is supplied in the case 

 of the mammal by the corpuscles in its own blood, most prob- 

 ably by the platelets which, as is well known, disintegrate very 

 rapidly when the blood is shed. The mammalian blood (dog) 

 may, however, be brought into the condition of the bird's blood 

 very easily by the so-called process of peptonization, that is 

 to say, by injecting rapidly into the circulation a certain amount 

 of a solution of Witte's peptone (see below, Antithrombin) . If 

 the injection is successful, <the blood when drawn remains fluid 

 for many hours, and, if promptly centrifugalized, the plasma may 

 fail entirely to clot. In such cases the addition of tissue extracts 

 may cause clotting within a few minutes, as in the case of the bird's 

 blood. The substance or substances in the tissues which exhibit 

 this accelerating influence upon clotting have received various names 

 from different observers in accordance with the special theory of 

 coagulation advocated. They have been called zymoplastic sub- 

 stances, thromboplastic substances, coagulins, cytozyms, thrombo- 

 kinase, etc. It is perhaps most convenient to speak of them in 

 general as thromboplastic substances, since this term does not com- 

 mit us to the manner of their action, but simply implies that they 

 are of importance in the formation of the clot. It has long been 

 known that thromboplastic substance may be extracted from the 

 tissues by the action of ether, or of alcohol and ether, and the 

 author* has shown that the active substance in the ether extracts 

 is one of the phosphatids, corresponding apparently to the sub- 

 stance which has been designated as cephalin. The closely related 

 lecithin has no thromboplastic power. In aqueous extracts of the 

 tissues the cephalin is held in solution in combination with a pro- 

 tein which is precipitated at a temperature of 60 C. It is probable 

 that this cephalin-protein constitutes the active thromboplastic 

 substance of the tissues. As regards the manner in which it par- 

 ticipates in the process of clotting several views have been pro- 

 posed. Two of these views are referred to in some detail in the 

 next paragraph. 



Theory of Coagulation. Modern theories of coagulation, with 

 some exceptions (Wooldridge, Nolf), accept as their starting-point 

 the fact that fibrin is formed eventually by the action of thrombin 

 upon fibrinogen. The various theories proposed differ from one 

 another largely in their explanation of the origin of the thrombin 

 and of the parts taken by the calcium and the thromboplastic 

 substances in the process of clotting. The simplest of these 

 theories assumes that the prothrombin in the blood arises from the 

 blood-plates (and leucocytes ?) and is activated to thrombin by 

 * Howell, "American Journal of Physiology," 31, 1, 1912, and 32, 264, 1913. 



