462 BLOOD AND LYMPH. 



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 Spiro f 

 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 

 and leucocytes, in mammalian blood, or of the cells of the wounded 

 tissues in the blood of the lower vertebrates, liberates thrombo- 

 kinase, which then, in combination with the calcium, converts the 

 thrombogen to thrombin. The theory may be expressed in dia- 

 grammatic form as follows: 



Cellular elements * thrombokinase 



Thrombokinase + calcium -f thrombogen = thrombin 



Thrombin + fibrinogen = fibrin. 



Morawitz has made no suggestion in regard to the chemical 

 nature of thrombokinase, but under this term he refers to the 

 active substance in tissue extracts, which has been explained in the 

 preceding paragraph as cephalin or a cephalin-protein compound. 



The theory explains very well many of the most significant 

 facts known in regard to clotting, but it may be said that the cen- 

 tral feature of the theory, the existence of an organic kinase, has 

 not been supported by direct experimental evidence. The author 

 has been led by his own work J to adopt a different point of view, 

 which may be expressed briefly, as follows: Prothrombin may be 

 converted to active thrombin by the action of calcium alone. 

 This activation does not occur in the circulating blood because an 

 inhibitory substance (antithrombin) is present in amounts sufficient 

 to prevent the reaction. In shed blood the tissue-cells or the cells 

 of the blood (plates) furnish a thromboplastic substance (cephalin- 

 protein) which neutralizes the action of the antithrombin and thus 

 permits the calcium to react with the prothrombin to form throm- 

 bin, which in turn reacts with the fibrinogen to form fibrin. Both 

 theories assume that the process of clotting in shed blood is 



* Morawitz, Hofmeister's "Beitrage," 5, 133, 1904, and "Arch. f. klin. 

 Med.," 79, 1. 



t Fuld and Spiro, "Hofmeister's Beitrage," 5, 174, 1904. 



j Howell, loc. tit. and "American Journal of Physiology," 29, 187, 1911. 



