COAGULATION. 463 



clotting. Another point of view is that the prothrombin is kept in- 

 active and the normal fluidity of the blood is maintained by the con- 

 stant presence of an antithrombin. That such a substance does exist 

 in the blood may be demonstrated by direct experiments. It has 

 long been known that extracts of the leech's head yield a soluble 

 protein which has, to a marked degree, the property of preventing 

 the clotting of blood. This substance is made in quantity for 

 experimental work, and is sold under the name of hirudin.* It 

 has been shown that this substance prevents thrombin from acting 

 upon fibrinogen, and in this sense, therefore, it is an antithrombin. 

 Moreover, the incoagulability of the blood of a so-called peptonized 

 dog is due to the presence in the blood of the same or of a similar 

 substance, which, according to the evidence at hand, is secreted 

 by the liver. When peptonized plasma is added to a mixture of 

 thrombin and fibrinogen, the normal action of the thrombin is 

 prevented, but if the peptonized plasma is first heated to 80 and 

 filtered from the heat coagulum formed, the filtrate no longer has 

 a restraining influence upon the action of thrombin. Evidently 

 the so-called peptonized plasma contains a something which an- 

 tagonizes the acton of thrombin, and the antagonistic reaction is 

 of a quantitative kind, that is to say, a fixed amount of the peptone 

 plasma will antagonize the action of a definite amount of thrombin. 

 This substance in the peptonized plasma behaves exactly like the 

 hirudin of the leech extract, and it is probable, therefore, that it is 

 a definite antithrombin. Moreover, by similar experiments with 

 the incoagulable plasma of the bird or with the oxalated plasma of 

 the mammal it can be shown that these bloods also contain anti- 

 thrombin. In the bird's blood this substance is present in larger 

 amounts than in the mammalian blood, but the evidence at hand 

 indicates that circulating blood contains constantly some anti- 

 thrombin and that this amount may be increased under certain 

 conditions, for example, by the injection of solutions of Witte's 

 peptone into the blood-vessels. As regards the antithrombin 

 present in normal human blood it is important to bear in mind 

 the fact that its action in antagonizing the thrombin is very much 

 greater at body temperatures than at room temperatures. At 

 about the body temperature its activity is greatly augmented. 

 In circulating blood, fibrinogen, prothrombin, calcium, and anti- 

 thrombin are present. The presence of the antithrombin prevents 

 the activation of the prothrombin, or if any is activated, prevents 

 it from reacting with the fibrinogen. When blood is shed there is 

 a general breaking down and disintegration of the platelets, which 

 results in adding two things to the blood: first, more prothrombin; 

 and, second, some thromboplastic substance which tends to neu- 

 * Franz, "Archiv. f. exper. Path. u. Pharmak.," 49, 342, 1903. 



