430 ^ BLOOD AND LYMPH. 



I 



constitutes the thrombin. This compound reacts with the fibrin- 

 ogen to form an insoluble calcium compound, the fibrin. This 

 theory may be expressed in simple form by an equation of this 

 kind: 



Ca nucleoprotein + fibrinogen = Ca fibrinogen. 

 (Thrombin.) (Fibrin.) 



Hammarsten has shown that the latter part of this theory is not 

 correct. Fibrin as ordinarily formed does contain much calcium, 

 but when a calcium-free solution of fibrinogen is brought into reac- 

 tion with a calcium-free ferment solution (blood-serum) a typical 

 clot is formed the fibrin of which is practically free from calcium. 

 This result also enables us to draw the important conclusion that 

 the calcium is not essential to the process of clotting after the 

 thrombin is once formed, and that therefore its role probably comes 

 in in the production of the thrombin. 



Some recent observers hold to the view that the active throm- 

 bin is formed from an inactive antecedent substance which is 

 designated usually as prothrombin. Schmidt and others believe 

 that the prothrombin exists preformed in blood-plasma and that 

 it may be converted into active thrombin by certain substances 

 arising from the blood corpuscles or indeed from many tissue cells. 

 These substances are described as zymoplastic substances (also 

 cytozyms, coagulins, or thrombokinases) . Others have considered 

 that the calcium salts constitute the efficient zymoplastic substance 

 that converts the prothrombin to thrombin, a view that is con- 

 tained in the first part of Pekelharing's theory, given above. 

 At present it would seem that the view advocated by Morawitz 

 explains best the numerous observations that are on record. 

 According to this author fibrin ferment results from the interaction 

 of three substances. One of these, corresponding in a general 

 way to a proferment, is found chiefly in the blood plates. When 

 these elements disintegrate, this substance, which the author desig- 

 nates as thrombogen, is liberated. Thrombogen alone cannot 

 convert the fibrinogen to fibrin. In order for it to produce this 

 effect it must be activated by the combined influence of calcium 

 salts and a thrombokinase. The latter substance, presumably 

 of an enzyme-nature, can be extracted from the tissue-elements 

 in general and in the blood may be obtained from the white or the 

 red corpuscles or the blood plates. The activated thrombogen 

 constitutes the fibrin ferment or thrombin which is capable of 

 converting the fibrinogen to fibrin. It would seem that in ordinary 

 clotting only a portion of the thrombogen is activated, so that 

 in the serum we find some thrombin and some thrombogen. This 

 belief is justified by the results of experiments made with the 



