36 A MANUAL OF PHYSIOLOGY 



prevents the clotting of blood both in the test-tube and when 

 injected into the circulation. The plasma obtained differs from 

 peptone plasma in refusing to coagulate unless tissue extract 

 is added. It is therefore deficient in thrombokinase, or, rather, 

 as has been shown, the kinase present is unable to act, because 

 neutralized by antikinase present in the leech-extract. Leech- 

 extract also contains an antithrombin, which can be neutralized 

 by a sufficient amount of thrombin. In the small wound from 

 which the leech sucks blood this sufficient amount is not 

 present, and the blood . remains unclotted, as it also does in 

 the alimentary canal of the leech. The anticoagulant sub- 

 stance, hirudin, has been isolated, and gives the reactions of 

 an albumose. 



Sources of Thrombogen and Thrombokinase. It has already 

 been stated that thrombogen exists in the circulating plasma. 

 This is shown by the fact that fluoride plasma obtained from 

 blood drawn directly through a wide cannula into sodium fluoride 

 solution, with all precautions to prevent alteration of the blood, 

 and immediately separated from the formed elements by the 

 centrifuge, will clot on the addition of tissue extract. The source 

 of the thrombogen has been thought to be the blood-plates, but 

 this has not been proved. Thrombokinase is not present in the 

 circulating plasma. In shed and clotting blood which has not 

 been allowed to come into contact with cut tissues the only 

 possible sources of thrombokinase, so far as we know, are the 

 corpuscles and the blood-plates. The red corpuscles we may 

 at once dismiss, for although the stromata, especially of nucleated 

 corpuscles, contain thrombokinase, or can under artificial con- 

 ditions be made to develop that action on coagulation by which 

 we recognize its presence, not only do they remain intact under 

 ordinary circumstances during coagulation, but there is strong 

 evidence, as has already been pointed out, that they do not 

 make any essential contribution to the process. We have left 

 over the leucocytes and the platelets, and it is highly probable 

 that from both thrombokinase is liberated in the first moments 

 after blood is drawn, and, acting on the thrombogen already 

 present in the plasma, changes it into actual fibrin-ferment. 

 This surmise is strengthened by the fact that in freshly-shed 

 mammalian blood extensive destruction of blood-plates takes 

 place. It has also been shown that the blood of the crayfish, 

 which coagulates with extreme rapidity, contains certain colour- 

 less corpuscles which, immediately it is withdrawn, break up 

 with explosive suddenness, and that substances which hinder the 

 breaking up of these corpuscles restrain coagulation (Hardy). 

 In the blood of another crustacean Limulus, the kingcrab, 

 coagulation is preceded by an agglutination of the leucocytes 



