COAGULATION OF THE BLOOD 345 



The prompt clotting which occurs when normal blood is shed is due 

 to something which is added to the blood when it comes into contact 

 with the lacerated tissues over which it flows, or which is derived 

 from the disintegration of the leukocytes or platelets in the shed blood. 

 This can be shown by employing the blood of Birds or Amphibians in 

 which the white corpuscles do not disintegrate so readily after shedding 

 as they do in the blood of mammalia. If a paraffined cannula be intro- 

 duced into an artery of a bird and the blood be collected in a paraffined 

 centrifugal tube and directly centrifugalized, the plasma which is 

 obtained either does not clot at all, or only very slowly. 



The plasma of birds' blood which is thus obtained may be induced 

 to clot if any of a large variety of tissue extracts, such as leukocyte 

 extract, or extracts of the brain, testes or thymus be added to it. The 

 active substance is soluble in ether and with difficulty soluble in 

 alcohol, and it contains phosphorus and nitrogen. Howell, and Mc- 

 Lean have shown that pure Kephalin, prepared from brain or other 

 tissues has the same power of inducing coagulation as the whole tissue 

 extract, while other phospholipins, lecithin, cuorin and sphingomyelin 

 are devoid of activity. The activity of kephalin is dependent upon 

 the presence of unsaturated linkages, for hydrogenated kephalin, or 

 kephalin that has become oxidized by exposure to the air, is inactive. 

 That some other factor besides the mere presence of unsaturated 

 linkages determines the action of kephalin is, however, evident from 

 the fact that the great majority of the phospholipins which are devoid 

 of Thromboplastic Action also contain unsaturated linkages. 



The prothrombin in oxalated birds' plasma is not converted into 

 thrombin by kephalin unless calcium salts are also present. Evidently 

 therefore, both of these factors cooperate in the transformation of 

 prothrombin into thrombin. 



Two views of the mode of action of thrombin upon Fibrinogen have 

 been advanced: The older view, originally proposed by A. Schmidt, 

 regarded thrombin as an enzyme which converted fibrinogen into 

 fibrin by hydrolysis, just as Casein is converted by rennet into Para- 

 casein. The foundation of this view was twofold: In the first place 

 the thrombin in the plasma or serum of shed blood is inactivated by 

 heating to 60 centigrade for a few minutes and the majority of the 

 enzymes are similarly inactivated at a like temperature. In the second 

 place very small quantities of thrombin are requisite to produce rela- 

 tively large quantities of fibrin. Howell, however, has adduced a 

 number of facts which militate against this view. In the first place 

 the apparent thermolability of thrombin is due to the presence of salts 

 or other substances in the plasma or serum, and pure thrombin, freed 

 from inorganic salts by dialysis, will withstand boiling for five minutes 

 or more without total loss of activity. If to the same solution 0.5 

 to 1 per cent, of sodium chloride be added, boiling for one minute 

 inactivates the thrombin completely. Of course this fact, in itself, 

 does not prove that thrombin is not an enzyme for, as we have seen, 



