850 PHYSIOLOGY 



The beginning of our modern ideas on the subject must be ascribed to Buchanan, 

 though many of the facts discovered by this observer escaped general recognition and 

 were later re-discovered by Alexander Schmidt. Buchanan worked chiefly on hydrocele 

 fluid and showed that this could be made to yield fibrin by treatment with fresh blood 

 or by adding it to the washings of a blood-clot. He compares the action of the latter 

 to that of rennet on the protein of milk. His experiments showed that ' fibrin has 

 not the least tendency to deposit itself spontaneously in the form of a coagulum, that, 

 like albumin and casein, fibrin often coagulates under the influence of suitable reagents, 

 and that the blood, like most other liquids of the body which appear to coagulate 

 spontaneously, only do so in consequence of their containing at once fibrin and sub- 

 stances capable of reacting upon it and so occasioning coagulation.' He held therefore 

 that the coagulation of the blood is due to the conversion of a soluble constituent of 

 the liquor sanguinis into fibrin by an action exerted probably by the colourless corpuscles 

 and comparable to the action which rennet exerts in effecting the coagulation of milk. 

 Furthermore, the liquid which accumulates in certain serous sacs may be made to yield 

 a coagulum of fibrin when subjected to the action of liquids or solids rich in the cellular 

 elements with which the coagulent action appeared to be associated (Gamgee). 



Denis in 1856 attpmpted 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 in 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 sub- 

 stances 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 conversion 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 interac- 

 tion between the opposing factors, some of which hinder and some of which favour 



