COAGULATION. 419 



the mammal, on the other hand, the blood itself contains all the 

 sources necessary for prompt coagulation. 



After the active thrombin is formed its manner of action upon the 

 fibrinogen is also a matter concerning which we have little positive 

 knowledge. Hammarsten has supposed that the thrombin causes 

 a splitting of the fibrinogen molecule, with the formation of the 

 insoluble fibrin and a soluble globulin, fibrin globulin, 



which can be found in small quantities in the serum after coagula- 

 tion. This conclusion has not, however, been demonstrated to be 

 correct. Some observers have suggested that the enzyme causes a 

 rearrangement in the structure of the fibrinogen molecule, while 

 others have given some reasons for believing that the action of the 

 thrombin is hydrolytic, as is the case with most of the enzymes of 

 digestion. Thus, Fuld * states, from experiments upon the blood- 

 plasma of birds, that the rapidity of clotting varies, not directly 

 with the amount of enzyme (thrombin) present, but rather in pro- 

 portion to the square root of the amount, thus following the law of 

 Schiitz for hydrolytic enzymes. 



Summary. By way of summary the following statements may 

 be made : The immediate factors necessary in coagulation are fibrin 

 ferment (thrombin) and fibrinogen. Calcium salts are also neces- 

 sary to the process of clotting, as it occurs in the blood, but it is 

 probable that they play some part in preparing the thrombin. It 

 is probable, also, that the formed elements of the blood, the blood 

 plates and leucocytes, furnish some constituent (zymoplastic sub- 

 stance) necessary to the preparation or activation of the thrombin. 

 We may provisionally adopt the view that thrombin is produced 

 from an antecedent prothrombin by the action of the calcium 

 salts and zymoplastic substance, according to the schema: 



Prothrombin + calcium salts + zymoplastic substance (thrombokinase) = 



thrombin. 

 Thrombin + fibrinogen = fibrin. 



In this last reaction the fibrinogen disappears entirely, so that none 

 is found in the serum after clotting. The thrombin, on the con- 

 trary, like other enzymes, is not destroyed in the reaction and is 

 found, therefore, in the serum of the clot. 



Why Blood Does Not Clot Within the Blood-vessels An- 

 tithrombin. The reason that blood remains fluid within the blood- 

 vessels and coagulates in a few minutes after being shed would seem 

 to be contained in the theories of coagulation just described. We 



* Fuld, "Beitrage zur chem. Physiol. u. Pathol.," 2, 514. 



