COAGULATION. 



459 



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 + thrombogen = thrombin 



Thrombm + 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 ex]>lains 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 

 lias 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 calcimn alone. 

 This activation does not occur in the circulating blood because an 

 inhibitory substance (antiprothrombin) 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 sub- 

 stance (cephalin-protein) which neutralizes the action of the in- 

 hibitory substance and thus permits the calcium to react with the 

 prothrombin to form thrombin, which in turn reacts with the 

 fibrinogen to form fibrin. If we use the term cephalin in place of 

 the more general expression thromboplastic substance or throm- 

 bokinase, this view can be expressed by the following schema: 



Prothrombin-antiprothrombin + Ca + cephalin = 



Prothrombin + Ca + cephalin-antiprothrombin 

 Prothrombin + Ca = thrombin. 



Both theories assume that the process of clotting in shed blood is 

 initiated by the production of a new substance, the thromboplastic 

 substance, furnished by the cells or blood-corpuscles (plates), 

 but on one view this substance acts as a kinase which participates 

 directly in the conversion of prothrombin to thrombin, while on 

 the other view the substance permits this conversion to occur 

 indirectly by neutralizing the opposing antiprothrombin. 



Several other theories of coagulation are proposed, but they are difficult 

 to explain in a few words. Two of the most recent of these theories may be 

 referred to briefly. According to Nolff the essential factors of coagulation 



* Howell, he. cit., and "American Journal of Physiology," 29, 187, 1911. 

 t "Archives internationales de physiol.," 6, 115, 1908. 



