COAGULATION. 461 



it may be supposed to act as a safety device. It is quite possible 

 that under normal conditions some thrombin may be constantly 

 formed in small quantities in the circulation, and that the pres- 

 ence of the antithrombin serves to prevent this thrombin from 

 acting on the fibrinogen. A second kind of inhibiting substance 

 as regards coagulation has been isolated from some of the organs 

 of the body, particularly the liver. This substance has no influence 

 upon the reaction between thrombin and fibrinogen, but it retards 

 or prevents the conversion of prothrombin to thrombin. It may 

 be designated, therefore, as an anti prothrombin. This substance 

 as isolated from the liver belongs apparently to the phosphatids 

 and has been given the distinctive name of heparin.* The 

 inhibitory influence of heparin upon the prothrombin is readily 

 antagonized by the action of tissue extracts (cephahn). It has 

 also the characteristic property that when added to serum or 

 plasma it causes a marked increase in the amount of antithrombhi. 

 If we assume in terms of the theory given in the preceding 

 paragraph that both antithrombin and antiprothrombin are pres- 

 ent normally in the circulating blood, this liquid will be ade- 

 quately protected from clotting. The antiprothrombin protects 

 against the formation of thrombin, while the antithroml^in gives 

 a further margin of safety by neutralizing any small amounts of 

 thrombin that may be formed under normal or unusual conditions. 

 Incoagulable Blood. — Certain substances when injected into 

 the circulation may make the blood wholly or partially incoag- 

 ulable. Some snake venoms have this effect, but the substance 

 whose action has been studied most carefully is the commercial 

 form of so-called peptone commonly designated as Witte's pep- 

 tone. If a solution of this substance made up in salt solution 

 (NaCl 0.9 per cent.) is injected directly into a vein in strengths oi 

 0.3 to 0.4 gm. per kilogram of animal it will be found that a speci- 

 men of blood taken within a few minutes either clots very slowly 

 or is entirely incoagulable. Such specimens can be made to clot 

 promptly by the addition of tissue extracts or solutions of purified 

 cephalin. The peptone solution has no direct effect upon the 

 coagulation, but when introduced into the circulation it sets up a re- 

 action in the hver through which an inhibitory material is furnished 

 to the blood. The nature of the reaction is not certainly known, 

 but it is usually stated that an antithrombin is produced. The 

 nature of the reactions given by the peptonized blood indicates, 

 however, that it is probably an antiprothrombin rather than an 

 antithrombin which is formed in the liver and given to the blood. 



Metathrombin. — In the serum of blood after clotting ready- 

 formed thrombin exists. On standing, the amount of this thrombin 



* Howell and Holt, "American Journal of Physiology, 47, 328, 1918. 



