456 BLOOD AND LYMPH. 



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- 

 servers have called attention to the fact that calcium salts in cer- 

 tain concentrations influence favorably the coagulation of blood. 

 We owe to Ai'thus and Pages, however, the proof that calcium 

 salts are essential to the process of normal coagulation. These 

 observers showed that freshly drawn blood allowed to flow into 

 an oxalate solution, in amounts such that the final concentration 

 in oxalate is not less than 0.1 per cent., will remain unclotted in- 

 definitely, but may be made to clot at any time b}^ the addition 

 of a suitable amount of calcium salt. Much discussion has ensued 

 in regard to the precise role played by calcium in the process of 

 clotting. The outcome of tliis work justifies the statement that 

 calcimn is not concerned in the final stage of clotting; namely, the 

 reaction between fibrinogen and thrombin, but takes an essential 

 part in the first stage, the conversion of prothrombin to thrombin. 

 According to the terminology used at present, we may say that 

 calcium is necessary for the activation of the thrombin. In the 



