42 THE CIRCULATING LIQUIDS OF THE BODY 



the effective thromboplastic substance in the tissues is a phos- 

 phatide, probably kephalin, united with protein. 



Intravascular Coagulation Regulation of the Clotting Process, 

 or Thrombotaxis. So far we have been considering the problem 

 of coagulation as if all the data for its solution could be 

 obtained by a study of the blood itself. In other words, our main 

 business up to this point has been the explanation of coagulation 

 in the shed blood; it has been only incidentally, and with the object 

 of casting light on the question of extravascular clotting, that we 

 have touched on the coagulation of the blood within the living 

 vessels. It is not possible here to adequately discuss, nor even to 

 define, the differences between the two problems. All we can do 

 is to warn the student, and to emphasize the warning by one or 

 two illustrations, that valuable as is the knowledge derived from 

 experiments on extravascular coagulation, it would be totally mis- 

 leading if applied without modification to the circulating blood. 

 For instance, we have recognized in the blood-plates an impoitant 

 source of the thrombokinase which plays so great a part in the 

 clotting of shed blood; but we may be sure that blood-plates are 

 constantly breaking down in the lymph and the blood, and we have 

 to inquire how it is that coagulation does not occur, except in 

 disease, within the vessels. Calcium is not wanting to the circu- 

 lating plasma, fibrinogen is not wanting, and it has already been 

 mentioned that thrombogen exists in perfectly fresh and, as we 

 may say, still living blood. Why, then, does it not coagulate ? 

 Some have said that coagulation is ' restrained ' by the contact of 

 the living walls of the bloodvessels; but although it is certain that 

 the contact of foreign matter and all dead matter is foreign to 

 living cells does hasten the destruction of blood-plates or that 

 alteration in them on which the liberation of the precursors of the 

 ferment depends, it is evident that it is just this ' restraining ' in- 

 fluence of the vessels, if it is due to anything more than the mere 

 smoothness of their endothelial lining, which has to be explained. 

 The best answer which can be given to the question is: First, that 

 the quantity of thrombokinase free in the plasma at any given time 

 must be small, since no evidence of its presence in fluoride plasma 

 can be obtained. If thrombokinase is liberated in the circulating 

 blood, we may assume that it is changed into some inactive sub- 

 stance, or quickly eliminated. And it appears that, unlike the true 

 ferments, thrombokinase acts quantitatively i.e., in proportion to 

 its amount upon thrombogen. Second, an antithrombin exists 

 in the circulating plasma, and even if fully formed fibrin-ferment 

 were present, it could not cause coagulation until the antithrombin 

 had been neutralized. This antithrombin is probably not manu- 

 factured in the blood, or at least not exclusively in the blood, but 

 in the tissues, and there is no reason to deny the vessels themselves 



