432 BLOOD AND LYMPH. 



be made: The immediate factors necessary in coagulation are fibrin 

 ferment (thrombin) and fibrinogen. Calcium salts are necessary 

 to the process of clotting as it occurs in the blood, but it is probable 

 that they play some part in preparing the thrombin. It is probable, 

 also, that the formed elements of the blood, the blood plates and 

 leucocytes, furnish the chief preliminary material from which 

 the thrombin is formed. We may provisionally adopt the view 

 that thrombin is produced from an antecedent thrombogen or 

 prothrombin which is derived from the blood plates. This is 

 converted into an active form by the influence of the calcium salts 

 present in the plasma and a thrombokinase which is furnished 

 by the plates or the leucocytes and can be obtained from the tissues 

 generally. The process may be represented schematically as 

 follows: 



Thrombogen + calcium salts + zymoplastic substance (thrombokinase) = 



thrombin. 

 Thrombin + fibrinogen = fibrin. 



In this last reaction the fibrinogen disappears entirely, so that none 

 is found in the serum after clotting. The thrombin, on the con- 

 trary, like other enzymes, is not destroyed in the reaction and is 

 found, therefore, in the serum of the clot, together with some throm- 

 bogen which has not been activated. The indefinite form in which 

 it is necessary to state this theory is in itself sufficient indication 

 of the amount of additional investigation which will have to be 

 made before we shall be in a position to explain satisfactorily 

 the entire history of the act of clotting. 



Why Blood Does Not Clot Within the Blood-vessels An- 

 tithrombin. The reason that blood remains fluid within the blood- 

 vessels and coagulates in a few minutes after being shed would seem 

 to be contained in the theories of coagulation just described. We 

 may assume that in the living blood-vessels the formed elements 

 leucocytes and blood plates do not disintegrate in great numbers 

 at a time, and therefore do not give rise to any noticeable quantity 

 of the antecedents of thrombin. It seems most probable that little, 

 if any, thrombin is actually present in the blood under normal 

 circumstances, and this in itself may be regarded as the main reason 

 for the fact that the blood remains unclotted. It is quite possible, 

 however, that other safeguards may exist in a matter" of such 

 prime importance. It has been shown, for instance, that, when 

 solutions of fibrin ferment (thrombin) are injected into the circu- 

 lation, clotting is not produced with the certainty that one might 

 expect. Delezenne has described experiments which indicate 

 that the liver exercises a defensive power in this respect.* He 

 states that when blood-serum containing, as it normally does, 

 * "Travaux de Physiologic/' Universite de Montpellier, 1898. 



