960 PHYSIOLOGY 



or solids rich in the cellular elements with which the coagulent action appeared 

 to be associated (Gamgee). 



Denis in 1856 attempted to separate this precursor of fibrin. He received 

 the blood into one-sixth of its volume of saturated sodium sulphate, allowed the 

 corpuscles to settle, and filtered off the supernatant plasma. On saturating this 

 with sodium chloride a precipitate was produced which Denis designated 

 ' plasmine.' This precipitate, on solution in water, slowly underwent coagulation 

 and was apparently split into two substances a solid fibrin and a soluble 

 protein. Clotting therefore, according to Denis, was dependent on the splitting 

 of a single protein into two different proteins, one of which was insoluble. A 

 few years later the subject was taken up by Alexander Schmidt, who devoted the 

 remaining thirty years of his life to the investigation of the coagulation of the 

 blood. Working first, as Buchanan had done, on fluids obtained from serous 

 cavities, he noticed that these could be made to clot by the addition of serum, 

 and he concluded that coagulation was due to the interaction or combination of 

 two different proteins, one fibrinogen, contained in the serous fluid, and the 

 other * fibrinoplastin,' which was contained hi the serum and could be precipitated 

 by acidification or by dilution and passage of a stream of carbon dioxide. This 

 fibrinoplastin was identical with what we should nowadays call paraglobulin, 

 but had adherent to it fibrin ferment. Schmidt later on found that in many 

 cases it was not sufficient to mix these two substances together, but that a third 

 factor was necessary, which could be obtained either from serum or from blood- 

 clot which had been coagulated by alcohol. This third factor he compared to a 

 ferment, so that the theory put forward by Schmidt in 1872 was that coagulation 

 depends on the interaction of two substances fibrinogen and fibrinoplastin 

 under the influence of a third substance, fibrin ferment or thrombin. A few 

 years later Hammarsten, of Upsala, in a very careful series of experiments, 

 proved conclusively that the fibrinoplastin of Schmidt was not a necessary 

 factor. Hammarsten discovered the method which we use at the present time 

 for separation of fibrinogen, namely, precipitation by half-saturation with 

 common salt, and showed that the fibrinogen obtained in this way and purified 

 by repeated precipitation and re-solution would yield a clot of fibrin on the 

 addition of fibrin ferment prepared by Schmidt's process. According to 

 Hammarsten, therefore, clotting was due to the converson of the fibrinogen 

 present in the circulating plasma into fibrin by the action of fibrin ferment, 

 which was probably yielded by the disintegration of the white blood-corpuscles. 

 Schmidt's later work was directed chiefly to determining the mode of origin of 

 the fibrin ferment. Though his researches yielded a number of important facts, 

 especially as to the part played by tissue-cells in furnishing the precursors of 

 the ferment or in influencing the processes of clotting, they did not result in 

 clarifying the views of physiologists generally on the subject of clotting. 

 Perhaps their most useful effect was to demonstrate the complexity of the 

 processes which occur in the blood after it leaves the vessels, and to show that 

 in the maintenance of the fluid condition in the vessels as well as in the production 

 of a clot outside the vessels there must be an interaction between the opposing 

 factors, some of which hinder and some of which favour the occurrence of 

 coagulation. According to Schmidt the plasma is itself derived from the cells 

 of the body, the fibrinogen being formed through the stages of paraglobulin 

 and cytoglobulin. The thrombin is derived from a precursor prothrombin 

 under the action of a zymoplastic substance also derived from the cells. In 

 the presence of the proper concentration of salts the thrombin acts upon 

 fibrinogen to produce fibrin. His views may be roughly expressed by the 

 following schema given by Howell : 



