CHAPTER XIII 

 BLOOD: BLOOD CLOTTING (Cont'd) 



THEORIES OF BLOOD CLOTTING 



Attempts to link all the foregoing facts together in the form of a 

 simple theory have not so far been entirely successful. All agree that 

 the fibrin is derived from fibrinogen by the action of thrombin, the points 

 in dispute being those which concern the origin of the thrombin and 

 the mode of action of the calcium and thromboplastic substances. The 

 theory most widely accepted in Europe is that of Morawitz, according 

 to which the thrombin exists in living blood in an inactive state called 

 thrombogen (prothrombin), which becomes converted into thrombin by 

 the simultaneous action on it of soluble calcium salts and of thrombo- 

 plastic substances furnished by the tissue cells in general and by the 

 cellular elements of the blood platelets and leucocytes. According to 

 this view the thromboplastic substance, aided by the presence of calcium 

 ions, converts thrombogen (prothrombin) to thrombin. It acts there- 

 fore as a kinase and is called thrombokinase. The fundamental fact of 

 this theory, then, is that kinase is necessary for the union of the cal- 

 cium with prothrombin a fact, however, which is challenged by Howell, 

 who states that prothrombin may be converted to thrombin by the action 

 of calcium ions alone. This investigator believes that the thrombo- 

 plastic substance acts not as a kinase but because it neutralizes anti- 

 thrombin, which is constantly present in the blood, and the function of 

 which is to prevent the calcium from uniting with the prothrombin to 

 form thrombin. Howell's theory in his own words is as follows: "In 

 the circulating blood we find as constant constituents fibrinogen, pro- 

 thrombin, calcium salts and antithrombin. The last named substance 

 holds the prothrombin in combination and thus prevents its conversion 

 or activation to thrombin. When the blood is shed, the disintegration 

 of the corpuscles (platelets) furnishes material (thromboplastin) which 

 combines with the antithrombin and'* at the same time liberates more 

 "prothrombin; the latter is then activated by the calcium and acts on 

 the fibrinogen." Antithrombin can also prevent the action of thrombin 

 on fibrinogen. As already pointed out, the thromboplastin can be de- 

 rived from the blood itself in the mammals, but only from the tissues 

 in the lower vertebrates. It is interesting to note that the thromboplastin 



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