COAGULATION OF THE BLOOD in 



That fibrin is not present in the blood before coagulation 

 had already been proved by Johannes Mu'ller (1831), but the 

 importance of his observations was not recognised until 

 some years later. Miiller placed frog's blood (in which 

 the corpuscles are four times as large as in human blood) 

 upon a filter-paper after diluting it with thin syrup to 

 delay coagulation. He found that the fluid (plasma) which 

 passed through the filter-paper completely unmixed with 

 corpuscles, clotted just as the whole blood would have done. 

 Clearly, therefore, a soluble antecedent of fibrin is present 

 in circulating blood. What is the antecedent, or what are 

 the antecedents, of fibrin? 



The key to this problem was provided by an extremely 

 ready observer, Andrew Buchanan (1830), who noticed that 

 accumulations of inflammatory lymph, which the surgeon is 

 called upon to "tap," sometimes coagulate after removal 

 from the body and at other times do not. Searching for 

 the cause of the clotting, he observed further that if during 

 the operation a little blood obtains access to it the lymph 

 clots. He therefore added to the lymph the several con- 

 stituents of the blood in order that he might ascertain the 

 real exciting cause. He found that the red corpuscles were ' 

 not necessary, since serum or even the washings from a 

 blood-clot would answer equally well. Indeed, it was not 

 necessary to use any of the constituents of blood. It is some- 

 times found that two exuded fluids, such as the lymph which 

 accumulates in the chest in pleurisy and that which accumu- 

 lates in the abdomen in dropsy, neither of which has any 

 tendency to clot when left to itself, will clot when mixed 

 together. Coagulation must therefore be due to the inter- 

 action of two substances. 



The problem now entered a chemical phase. Denis (1859), 

 when investigating the proteid (albuminoid) constituents of 

 blood, found that if he saturated plasma (blood from which 

 the corpuscles have been removed before clotting) with sodic 

 sulphate, a sticky mass was precipitated which, when re- 



