THE CIRCULATING LIQUIDS OF THE BODY 39 



coagulation is especially striking in birds on injection of tissue 

 extracts. 



To a certain extent the action of nucleo-protein in coagula- 

 tion can be imitated by other substances of animal origin, such 

 as the venoms of some vipers (Martin), and even by certain 

 artificial products of the laboratory, the synthesized colloids of 

 Grimaux, which, when injected into the blood, produce the same 

 phenomena of intravascular coagulation down to the finest detail 

 and including the negative phase. It is not known whether these 

 substances act on the blood-plates, leucocytes, or other cells, 

 and thus cause an increased production or an increased liberation 

 of one or more of the precursors of fibrin-ferment, or whether 

 they take part directly in its formation. But there is some 

 evidence that the venoms which favour coagulation do so in 

 virtue of their containing a kinase. On the other hand, cobra- 

 venom prevents coagulation by means of an antikinase that is, 

 a substance which antagonizes the action of kinase, and so 

 hinders the formation of fibrin-ferment. It does not contain 

 an antithrombin that is, a body which will prevent the action 

 of fibrin-ferment already formed (Mellanby). 



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 our warning by one or two illus- 

 trations, that valuable as is the knowledge derived from experi- 

 ments on extravascular coagulation, it would be totally mis- 

 leading if applied without modification to the circulating blood. 

 For instance, we have recognized in the leucocytes and blood- 

 plates an important source of the thrombokinase which plays so 

 great a part in the clotting of shed blood ; but we may be sure 

 that leucocytes and 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 circulating 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 



