THE -COAGUEATION “OF. THE BLOOD 61 
into fibrin, and the latter body is certainly not a calcium 
compound of the former. A series of analyses confirmed this, 
since it was shown that the calcium content of fibrin is not 
higher than the fibrinogen which yielded it, and fibrin can be 
produced which contains only a trace of lime—o’0o7 to 00095 
per cent. However, the absolute proof that calcium does take 
a specific part in the formation of fibrin-ferment, as Pekelharing 
believed, was confirmed by Hammarsten, since the material 
separated from cooled oxalated plasma contained a zymogen 
which could be directly and specifically activated by calcium 
salts, and induce coagulation of fibrinogen solutions, a property 
it did not possess unless these salts were added. Calcium salts 
or calcium ions, therefore, play an essential role in the first 
phase of the coagulation process by activating a zymogen. In 
this way thrombin, non-existent in living blood, originates in 
blood after it is shed. The absolute amount of calcium present 
is stated by Sabbatani’ to be a negligible factor for the formation 
of thrombin. Only that portion which is in the ionic state is 
concerned in the process. The arguments for this view are 
that all physical methods which, like heat and cold, exalt or 
depress the amount of ionisation or affect the velocity of the 
ions, equally affect, accelerate, or retard the onset of coagulation. 
In the case of fluoride-plasma, which clots simply on the 
addition of water, the dilution may promote a sufficient degree 
of ionisation of the suspended lime salts. 
6. THROMBIN OR FIBRIN-FERMENT 
The interest attaching to this part of the question may be 
grouped around the three following facts : 
1. The production of intra-vascular clotting by the injection 
of various tissue-extracts, and the development of a clot mm 
vitro from non-coagulable or feebly coagulable liquids by the 
addition of tissue-extracts. 
2..The discovery of Delezenne that the blood of those 
vertebrates which possess nucleated red corpuscles often does 
not spontaneously clot. Blood removed from birds such as the 
goose or pigeon with every aseptic precaution will yield a 
clear plasma which may actually commence to putrefy before 
it coagulates. 
' Arch. ital, de Biologie, xxxix. 1, p. 333. 
