COAGULATION. 459 



glands. When the blood is shed, or under certain abnormal condi- 

 tions while circulating in the vessels, the prothrombin is changed 

 or activated to thrombin. The nature of this change is discussed 

 below. Once the thrombin exists in active condition it exhibits 

 the remarkable property of precipitating the fibrinogen in the form 

 of a gelatinous clot, the essential part of the clot being a mesh of 

 fibrin needles. 



Nature of the Action of the Thrombin on Fibrinogen. Solu- 

 tions of fibrinogen may be precipitated readily in a number of ways, 

 but, so far as known, only 'thrombin is capable of precipitating it 

 in the peculiar way necessary to form a gelatinous clot. The 

 nature of this reaction is obscure. The usual view in physiology 

 is that first suggested by Schmidt, namely, that the thrombin is 

 an enzyme or ferment, fibrin ferment. If this view is correct, then, 

 in accordance with our idea of the way in which ferments act, the 

 thrombin should not be used up in the reaction, but should act 

 over and over again, converting new fibrinogen to fibrin. Moreover, 

 the fibrin on this view should be formed entirely from the fibrinogen, 

 since the thrombin, if a ferment, does not constitute a part of the 

 final product. Several specific hypotheses have been proposed to 

 explain the nature of the change undergone by the fibrinogen 

 in its conversion to fibrin. It has been suggested that the fibrino- 

 gen undergoes a hydrolytic cleavage, with the formation of the 

 insoluble fibrin, on the one hand, and a soluble " fibrin globulin," 

 on the other; or that the molecular state of the fibrinogen undergoes 

 a change similar perhaps to that caused by heating, whereby an 

 insoluble product is formed. These and similar hypotheses have 

 not been supported by experimental evidence, and, indeed, a number 

 of observers from time to time have questioned the fundamental 

 part of such theories, namely, the belief that thrombin acts like a 

 ferment. Experiments indicate that, unlike the ferments in general, 

 thrombin under certain conditions (absence of salts) withstands 

 the temperature of boiling water, and, again, unlike the ferments, 

 a small amount of thrombin allowed to act upon fibrinogen pro- 

 duces a fixed amount of fibrin which does not increase with the 

 time during which the thrombin is allowed to act. It has been 

 suggested, therefore, as an alternative hypothesis that the throm- 

 bin and fibrinogen form a combination of a physical or physico- 

 chemical character which results in their mutual precipitation as 

 fibrin (Nolf ) . Such a theory is in accord with the fact that freshly 

 formed fibrin when subjected to prolonged washing with water 

 gives off little or no thrombin, but when subsequently treated with 

 solutions of sodium chlorid (8 per cent.) a portion of it goes into 

 solution and this solution is rich in thrombin. 



The Influence of Calcium Salts in Coagulation. Many ob- 



