THEORIES OF CO A G ULA TION. 1 7 3 
residue after gastric digestion of its solution, showing that it at Least, 
as above Btated, contains some nucleo-proteid. Probably this is an 
accidental contamination. 
Production of intravascular coagulation of blood and of uncoagulable 
blood. — It was discovered by Edelberg 1 that intravenous injection of 
Schmidt's fibrin ferment may produce thrombosis in the vense cava?, 
the right side of the heart, and the pulmonary arteries. Foa and 
Pellacani - showed that the same will occur with extracts of various 
organs. The same fact was independently noticed by Wboldridge, 3 
who found that a substance or substances obtainable from saline extract 
of lymphatic glands, thymus, testicle, and other glandular organs, tend to 
produce, when injected rapidly in sufficient amount into the veins of 
animals, instant coagulation of the blood whilst still within the blood 
vessels. On the other hand, if injected more slowly, or in insufficient 
amount to produce intravascular coagulation, the coagulability of the 
blood in vitro becomes abolished ; this condition was termed by Wool- 
dridge the " negative phase." When the negative phase is once obtained, 
a very large dose of the material fails to produce intravascular clotting. 4 
Wooldridge gave the name " tissue fibrinogens " to the substances thus 
extracted, and more extended knowledge has led to the general recog- 
nition of the fact that they belong to the class of nucleo-albuniins or 
nucleo-proteids. The coagulation when it occurs is found, first, in the 
portal venous system ; then in the general venous system, and pulmonary 
arteries and in the right side of the heart ; and finally, when the effect 
is most pronounced, in the general arterial system ; but rarely in the 
pulmonary veins. Its occurrence is assisted by an excess of C0 2 in the 
blood. 5 Albino rabbits and the Norway hare in its albino condition are 
immune to these effects (Pickering). 
It has been supposed by Lilienfeld ° that this action of the nucleo- 
proteid in causing coagulation is due to the nuclein or nucleic aeid 
which it contains, and that, when the negative phase is obtained, this 
result is due to the action of the proteid part of the molecule of 
nucleo-proteid in preventing coagulation. This hypothesis is rendered 
improbable by the observations of Halliburton and Pickering, 7 who 
found that intravascular coagulation can be readily obtained in rabbits 
by intravenous injection of artificial colloids (containing no nucleic 
acid). 8 These colloids likewise yield the negative phase (retardation of 
coagulation), if injected in quantity insufficient to produce coagulation ; 
and, as with solution of nucleo-proteids, they are without action upon 
albino rabbits. Xevertheless, like solutions of nucleo-proteid, they 
hasten the coagulation of the blood of other animals, if mixed with it 
in vitro. These observers also found that the retarding influence of 
1 Arch. f. exper. Path. u. Pharmakol., Leipzig, 1880, Bd. xii. S. 283. 
2 Riv. clin. di. Bologna, 1880, p. 241. 
3 Proc. Roy. Soc. London, 1886. See also ''Die Gerinnung des Blutes," Leipzig, 1S91. 
4 Wooldridge, Arch. f. Physiol., Leipzig, 1888. 
5 Wright, Journ. Physiol., Cambridge and London, vol. xii. 6 Loc cit. 
7 Journ. Physiol., Cambridge and London, 1895, vol. xviii. pp. 54 and 285 ; Pickering, 
Proc. Roy. Soc. London, 1S96, vol. lx. p. 337. 
8 The artificial colloids investigated were prepared by Grimaux's methods (C'ompt. rt nd. 
Soc. dc liol., Paris, 1SS1, tome xciii. p. 771; 1884, "xcviii. pp. 105, 1434, and 1578). 
Their chemical properties and mode of preparation have already been described by Professor 
Halliburton in a previous article (p. 36). It is possible that they may act, not directly, 
but by setting free nucleo-proteid from the white corpuscles. Their solutions do not, 
however, cause disintegration either of the red or white corpuscles, nor any apparent 
change in the epithelium of the vessels. 
