THEORIES OF COAGULATION. 169 
globulin dues not take part in forming fibrin. By precipitating fibrin- 
ogen by half-saturating plasma w i 1 1 1 sodium chloride, he obtained it 
free from serum globulin, and found that its solution in dilute salt 
solution was coagulated by the addition of Schmidt's extract — the so- 
called fibrin fermenl —alone. Hammarsten proved that coagulation 
consists in a conversion of fibrinogen into fibrin; the change being 
accompanied by a splitting of the fibrinogen, and not by a combination 
of it with the serum globulin, as was supposed by Schmidt. 
Influence of lime salts. — Theories of Frt und and of Arthus and Pages. 
— The more recent researches since these of Hammarsten have been 
in the direction of elucidating the true nature of the substances 
contained in Schmidt's extract. Green 1 found the extract to contain 
sulphate of lime, and that if lime were removed from plasma by 
dialysis its coagulability became lost, but w T as restored by the addition 
of sulphate of lime. Ringer and Sainsbury 2 showed that other salts of 
lime, such as calcium chloride, might replace the sulphate, and that the 
calcium might be replaced by barium and by strontium, although the 
salts of these metals are not so efficacious as the corresponding salts 
of calcium. 
Freund 3 also drew special attention to the important part played by 
lime salts in promoting the formation of fibrin. He supposed the 
original cause of the deposition of fibrin in fibrinogenous liquids to be 
the formation of insoluble tribasic phosphate of lime, by the interaction 
of soluble phosphates (which he supposed to be shed out from the 
corpuscles whenever they come in contact with and adhere to foreign 
surfaces ) with soluble lime salts contained in the plasma ; the lime 
phosphate combining at the moment of formation with fibrinogen, and 
forming fibrin, and no other agency in the shape of a special ferment 
being necessary. This inference has not, however, been confirmed by 
subsequent observers. Freund supposed neutral salts, peptone, etc., to 
act in preventing coagulation, by keeping phosphate of lime in solution, 
and the walls of the blood vessels to act in preventing coagulation 
because the corpuscles do not adhere to them. Freund based his theory, 
partly upon the fact that if blood is drawn from an artery through a 
tube smeared with oil or vaseline into a vessel similarly prepared, the 
blood remains fluid for a long time, presumably because the adhesion of 
the corpuscles to the walls does not occur. Similar experiments with 
blood kept surrounded 1 >y paraffin or oil were performed by Haycraft 
with like result. 4 
Arthus and Pages 5 mixed blood as it flowed from the vessels with a 
small quantity of a soluble oxalate 6 (0*07-0T parts per 100 of blood) 
sufficient to precipitate the lhne salts dissolved in the plasma. They 
found that blood thus treated did not coagulate, however long it might 
be kept, 7 but that coagulability of its plasma is immediately restored on 
again adding a soluble lime salt, such as calcium chloride. They 
1 Journ. Physiol., Cambridge and London, 1887, vol. viii. p. 354. 
2 Ibid., 1890, vol. xi. p. 369. 3 Med. Jalvrb., Wein, 1888, S. 259. 
4 Journ. Anat. and Physiol., London, 1888, p. 172 ; Haycraft and Carlier, ibid., p. 582. 
5 Arch, de physio!, norm, et path., Paris. 1890, p. 739 ; Arthus, These de Paris, 1892. 
6 Solutions ot soap (0 - 5 parts per 100 of blood) or of soluble fluorides (0 - 2 parts per 100 
of blood) act similarly to those of oxalate. 
7 Hammarsten makes a similar statement for horse's blood, but it is certainly not 
correct for all kinds of blood. Oxalate plasma, obtained from dog's or sheep's blood, does 
undergo coagulation on standing ; coagulability is therefore not abolished by precipita- 
tion of the lime by oxalate, but merely deferred. "We shall return to this point immediately. 
