950 PHYSIOLOGY 



to the glass rod used for stirring. This mass can be taken out 

 of the fluid, washed by kneading with half-saturated sodium 

 chloride solution, and then redissolved by the addition of distilled 

 water. With the salt adhering to the precipitate a dilute saline fluid 

 is formed in which the fibrinogen is soluble. The fibrinogen can be 

 purified by repeating the precipitation and solution, though it tends 

 to lose its solubility in the process, so that purification is always 

 attended with some loss. The solution of fibrinogen thus obtained is 

 perfectly clear and colourless. On warming, practically the whole of 

 its protein is thrown down between 56 and 60 C. The same precipi- 

 tate is produced on heating the original plasma, whereas serum 

 obtained by the expression of the clot does not give any precipitate on 

 heating until a temperature of 68 to 70 C. is reached. If a solution 

 of fibrinogen, obtained by precipitating with sodium chloride and 

 dissolving in distilled water, be treated with a drop or two of calcium 

 chloride it rapidly clots with the formation of typical fibrin. We might 

 conclude from this experiment that fibrin was a compound produced 

 by the union of calcium salts with fibrinogen. Further experiments 

 show, however, the untenability of this hypothesis. If the fibrinogen 

 has been thoroughly purified by repeated precipitation and re-solution, 

 calcium salts are found to have entirely lost their power of causing 

 coagulation. Such a purified fibrinogen can still be made to clot by 

 the addition either of serum or of the washings of a blood-clot, or of 

 the watery extract of alcohol-coagulated serum. This power of serum 

 to convert fibrinogen into fibrin is due to the presence in it of minute 

 quantities of a substance which has been designated as ' fibrin 

 ferment ' or thrombin. It has been regarded as a ferment because it 

 is active in minimal quantities and is stated not to be appreciably 

 used up in the process of clotting. Thus if we add some serum to a 

 fibrinogen solution we can cause clotting, and then on squeezing the 

 clot obtain a serum which will bring about coagulation when added to 

 a fresh portion of fibrinogen. Considerable doubt, however, has been 

 thrown on the ferment nature of thrombin by the recent work of 

 Kettger in Howell's laboratory. Rettger shows, in the first place, that 

 the statement of the preceding sentence is only true if a large excess 

 of thrombin solution be made use of in the first instance. If small 

 quantities of thrombin solution be added to large quantities of plasma 

 or of pure solutions of fibrinogen, the amount of fibrin obtained is 

 proportional to the amount of thrombin added. This is shown in 

 the following experiment : 



5 drops of thrombin gave 0-2046 grm. fibrin. 

 10 0-3573 



20 0-6089 



40 1-5872 



