BLOOD. 357 



baring, the nucleo-proteid first combines with the calcium, and then this cal- 

 cium compound reacts with the fibrinogen, transferring its calcium to a portion 

 of the molecule. We might say, therefore, that there are three fibrin factors 

 fibrinogen, nucleo-proteid, and calcium salts ; the first and last of these exist 

 in the circulating blood, but the uucleo-proteid is formed usually only after 

 the blood is shed, and is derived from the disintegration of the formed ele- 

 ments, the leucocytes and blood-plates. How these three factors interact to 

 form fibrin cannot be stated positively, but it seems to be satisfactorily deter- 

 mined that the fibrin is a compound of calcium with a product derived from 

 the splitting of the fibrinogen. 



Nature and Origin of Fibrin Ferment (Thrombin). Recent views as 

 to the nature of fibrin ferment have been referred to incidentally in the 

 description of the theories of coagulation just given. The relation of these 

 newer views to the older ideas can be presented most easily by giving a 

 brief description of the development of our knowledge concerning this body. 

 Schmidt prepared solutions of fibrin ferment originally by adding a large 

 excess of alcohol to blood-serum and allowing the proteids thus precipitated 

 to stand under strong alcohol for a long time until they were thoroughly coagu- 

 lated and rendered nearly insoluble in water. At the end of the proper period 

 the coagulated proteids were extracted with water, and there was obtained a 

 solution which contained only small quantities of proteid. It was found that 

 solutions prepared in this way had a marked effect in inducing coagulation 

 when added to liquids, such as hydrocele liquid, which contained fibrinogen, 

 but which did not clot spontaneously or else clotted very slowly. It was after- 

 ward shown that similar solutions of fibrin ferment are capable of setting up 

 coagulation very readily in so-called salted plasma that is, in blood-plasma 

 prevented from clotting by the addition of a certain quantity of neutral salts. 

 It was not possible to say whether the coagulating power of these solutions 

 was due to the small traces of proteid contained in them, or whether the pro- 

 teid was merely an impurity. The general belief for a time, however, was 

 that the proteids present were not the active agent, and that there was in solu- 

 tion something of an unknown chemical nature which acted upon the fibrinogen 

 after the manner of unorganized ferments. This belief was founded mainly 

 upon three facts : first, that the substance seemed to be able to act powerfully 

 upon fibrinogen, although present in such minute quantities that it could not be 

 isolated satisfactorily ; second, it was destroyed by heating its solutions for a few 

 minutes at 60 C. ; and, third, it did not seem to be destroyed in the reaction 

 of coagulation which it set up, since it was always present in the serum squeezed 

 out of the clot. Schmidt proved that fibrin ferment could not be obtained 

 from blood by the method described above if the blood was made to flow im- 

 mediately from the cut artery into the alcohol. On the other hand, if the shed 

 blood was allowed to stand, the quantity of fibrin ferment increased up to 

 the time of coagulation, and was present in quantity in the serum. Schmidt 

 believed that the ferment was formed in shed blood from the disintegration 

 of the leucocytes, and this belief was corroborated by subsequent histological 



