464 BLOOD AND LYMPH. 



desired to render the blood of an animal incoagulable. A substance 

 having a similar action exists in blood. Its chemical nature is not 

 known, so that it must be designated by the general term "anti- 

 thrombin." The quantity present in any given specimen of blood 

 may be estimated with some degree of exactness by ascertaining the 

 extent of its retarding or inhibitory power when a definite amount 

 of plasma is added to a known mixture of thrombin and fibrinogen. 

 Experiments of this kind have shown that in the blood of birds and 

 reptiles which clots slowly (provided it does not come into contact 

 with the tissues) more antithrombin is present than in the blood of 

 the mammal. In dog's blood the normal amount of antithrombin 

 may be increased greatly by the process of peptonization. This 

 process consists in injecting into the circulation a strong solution of 

 Witte's peptone in amounts equal to 0.3 to 0.4 gram per kilogram of 

 animal. The result of the injection is to render the dog's blood in- 

 coagulable for a time, and this effect seems to be explained by the 

 large increase in antithrombin. Peptonized blood may be made to 

 clot by the addition of a solution of cephalin or of the extract of a 

 tissue. It has been suggested that the normal fluidity of the cir- 

 culating blood is dependent in the first instance upon the protecting 

 influence of the antithrombin, and that when the blood is shed the 

 antithrombin is neutralized by the thromboplastic substance 

 (cephalin) liberated by the disintegration of the platelets or fur- 

 nished by the surrounding wounded tissue. The whole matter of 

 the cause of the normal fluidity of the blood is complicated some- 

 what by the discovery that other substances are formed in the 

 body (liver, heart, etc.) which retard or prevent coagulation not, 

 as in the case of antithrombin, by preventing a reaction between 

 thrombin and fibrinogen, but by opposing the activation of pro- 

 thrombin to thrombin.* In other words, we have to recognize the 

 existence of an antiprothrombin as well as an antithrombin. The 

 latter is known to occur normally in the blood, but whether the 

 former is also present in blood has not been determined. The sub- 

 stance which has an antiprothrombin action belongs chemically to 

 the phosphatids, but the chemical nature of the antithrombin is 

 unknown. Doyon f believes that it is a nucleic acid compound, but 

 this view is not in accord with the facts known in regard to the anti- 

 thrombin of blood. Delezenne, Wolf, and others t have published 

 experiments which indicate that the blood antithrombin is formed 

 in the liver. 



Metathrombin. In the serum of blood after clotting ready- 

 formed thrombin exists. On standing the amount of this thrombin 



* Howell, "Harvey Lectures," 1916-17. 



t Doyon, "Comptes. rend, de la Soc. de Biologic," 1911-13. 



j Denny and Minot, "American Journal of Physiology," 38, 233, 1915. 



