COAGULATION 25 



Thrombin was at one time universally believed to be a 

 ferment. There is evidence, however, that thrombin 

 unites quantitatively with fibrinogen. It is probably a 

 protein. 



We have already seen that when blood is drawn direct 

 from the blood-vessel into a vessel fined with paraffin — that 

 is to say, without touching any tissue — clotting is retarded. 

 In the bird, under the same circumstances, it is prevented 

 altogether. In blood drawn in this way, clotting can be 

 readily induced by addition of almost any tissue-extract, 

 or of blood-clot. But if tissue-extract is added to pure 

 fibrinogen, clotting does not occur. The substance present 

 in tissue-extract is therefore not thrombin, though its 

 presence is necessary for the formation of thrombin. In 

 the formation of thrombin, therefore, two factors are neces- 

 sary, calcium and the substance present in tissue-extract. 

 The latter is a ferment called thrombokinase. Thrombo- 

 kinase, in addition to being present in tissues, occurs also 

 in the blood platelets, or rather, it would be more accurate 

 to say, is produced in the formation of the platelets. The 

 absence of platelet-formation in the bird is the reason why 

 uncontaminated blood does not clot in these animals. 



The argument may be summarised thus : clotting takes 

 place in two stages : (1) the formation of thrombin from 

 thrombogen (present in plasma), by the action of the ferment 

 thrombokinase (present in tissues and blood-platelets), in 

 the presence of calcium. (2) The interaction of thrombin 

 and fibrinogen to form fibrin. 



The view has been expressed that thrombokinase is not 

 a specific substance, the formation of thrombin being attri- 

 buted to the effect of the calcium ions upon the colloidal 

 thrombogen in the presence of any fine particles, such as 

 dust. 



To explain why clotting does not occur in the intact 

 circulation, we must assume ' either that the endotheUal 

 fining of the vessels is devoid of thrombokinase, or that 

 an antithrombin is present. A similar hypothetical anti- 



