PROTEINS 495 



exclude this possibility. The molecular concentration of the 

 active substance may be so minute that enough free Ca++ is 

 still left in solution to form thrombin. Calcium is not a stoichio- 

 metric constituent of the fibrin formed by the action of the 

 thrombin upon fibrinogen. (It is interesting to note that the 

 action of calcium is specific and that while other bivalent cations 

 such as barium and strontium have an effect, it is very slight 

 compared with that of calcium.) 



The platelets appear to liberate a substance that greatly 

 hastens coagulation. Whether or not they are indispensable is 

 unknown. Although coagulation may take place even when no 

 platelets are present, this may be due to the presence of dis- 

 integrated platelet material. The blood of birds has very few 

 platelets ; its plasma coagulates poorly. The addition of platelets 

 from the blood of any other animal hastens coagulation. When 

 blood is withdrawn from the body, the platelets disintegrate 

 rapidly and in so doing presumably set free a substance that 

 functions as a catalyst in hastening coagulation. In the human 

 disease known as purpura hemorrhagica, there is platelet defi- 

 ciency. Coagulation occurs but is retarded. Further evidence 

 is to be had in that clot retraction, for which platelets are 

 essential, does not occur in purpura. 



The fourth substance actively involved in blood coagulation, 

 being the third of the trio which, combined, constitute thrombin, 

 is the unknown plasma substance which has been termed 

 thrombogen, or prothrombin. Little is known of its action 

 other than that it appears to be the true precursor of thrombin 

 activated by calcium and platelets. 



The mechanism of blood coagulation in general is regarded 

 by some as comparable to the coagulation of proteins by enzymes, 

 such as the coagulation of milk by rennin. 



Human beings known as bleeders suffer from hemophilia, a 

 condition preventing the coagulation of blood when it reaches the 

 surface of a wound. It is a heritable quality transmitted solely 

 by women, in whom it is suppressed (as a recessive character) ; 

 only men suffer from it. Its cause is unknown, but it may be 

 due to stability of the platelets, thus preventing the liberation 

 of their active coagulating principle ; possibly it is due to retarded 

 activation of prothrombin. 



