458 BLOOD AND LYMPH. 



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 

 the calcium, the thrombin then reacting with the fibrinogen. The 

 theory which seems to be most generally accepted at present is 

 that proposed independently by Morawitz* and by Fuld and Spirof 

 Using the terminology of Morawitz, this theory assumes that the 

 thrombin is present in the blood in an inactive form which he 

 designates as thrombogen. To convert this thrombogen (pro- 

 thrombin) to thrombin requires the action both of calcium salts 

 and of an organic thromboplastic substance which he designates 

 as a kinase or thrombokinase. Thrombokinase is furnished by the 

 tissue-cells in general, especially by those rich in nuclein, and is 

 furnished also by the cellular elements of the blood. In the cir- 

 culating blood calcium salts and thrombogen are present, but no 

 kinase. When the blood is shed the disintegration of the platelets 



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

 t Morawitz, "Hofmeister's Beitrage," 5, 133, 1904, and "Arch. f. klin. 

 Med.," 79, 1. 



JFuld and Spiro, "Hofmeister's "Beitrage," 5, 174, 1904. 



