170 THE BLOOD 
inferred that the presence of a soluble salt of lime is necessary to the 
formation of fibrin, which, according to them, is produced by a combina- 
tion, under the influence of fibrin ferment, of a part of the fibrinogen 
with lime, the remainder of the fibrinogen — which is assumed to split 
into two parts — forming a globulin coagulating at 64° 0. (Hammarsten's 
fibrino-globulin). 1 
Whilst it would appear from these researches that soluble lime salts are 
necessary to the formation of fibrin, 2 it has been shown by Home that the 
presence of a slight excess of these salts and also those of barium and strontium 
will hinder or, in great amount, entirely prevent its formation ; their action 
being far more marked in this respect than that of other neutral salts, which 
require to be mixed in much greater amount with blood to prevent its co- 
agulation. 3 The reason for this is probably to be found in the fact that fibrin 
is soluble to some extent in neutral salts of a certain strength (including salts 
of calcium, barium, and strontium). 
Influence of nucleo-proteid. — Theory of Pekclhariny. — Halliburton 4 and 
Pekelharing 5 both obtained from Schmidt's extract a body giving proteid 
reactions, and resembling in many particulars the globulins, to which 
class of proteids they at first regarded it as belonging. 6 They showed 
that the ferment action of Schmidt's extract is intimately dependent 
upon the presence of this substance, which could also, as Halliburton 
showed, be obtained from lymphatic glands. Halliburton termed it 
cell globulin ; subsequently both observers recognised the fact that the 
substance in question was not a true globulin but a nucleo-proteid. 7 
According to Pekelharing, it possesses the property of combining with 
lime, which it does not yield to distilled water by dialysis, nor is the 
combination broken up by soluble oxalates, although these, if present 
from the first, may prevent the original combination. The albumose in 
commercial peptone also prevents such combination, the albumose itself 
combining with the lime salts present ; 8 if these are in excess, " peptone " 
does not prevent coagulation from taking place. The lime combination 
of nucleo-proteid is, according to Pekelharing, the body which has been 
known as fibrin ferment (thrombin). It can be formed not only from 
the nucleo-proteids contained in plasma or serum, but also from nucleo- 
proteids in the cells of the thymus, testicle, and other glands, by 
1 Arthus and Pages found that strontium can replace lime in this reaction, but that 
barium and magnesium cannot. Ringer and Sainsbury have, however, shown that barium 
may take the place cflime in promoting coagulation, although it is less powerful (Journ. 
Physiol., Cambridge ami London, 1890, vol. xi. p. 369). They also found that the salts of 
sodium and potassium act antagonistically to those of lime, barium, and strontium. 
2 A. Schmidt, even in his last communication upon the subject ("Weite re Beitr. z. 
Blutlehre," Wiesbaden, 1895), denied altogether that lime salts have any specific action 
or differed from other neutral salts, and considered that the addition of a soluble oxalate to 
blood acts either by preventing the formation of fibrin ferment or by hindering the action 
of ferment, if present, on fibrinogen. Cf., however, Arthus, Arch, dc physiol. norm, d 
path., Paris, 1896, and Hammarsten, loc. '-it. 
3 Journ. Physiol., Cambridge and London, 1896, vol. xix. p. 356. Wright also noticed 
the fact that considerable excess of calcium added to oxalate blood prevents coagulation, 
Journ. Path, and Baeteriol., Edin. and London, 1893, vol. i. p. 434. 
4 Proc. Boy. Soc. London, 1888, vol. xliv. p. 255. 
: ; Festschr. Rudolf Virchow, Berlin, 1891, S. 435. 
u Lilienfeld has recently repeated this error. Ztschr. f. •physiol. L'licm., Strassburg, 
Bd. xx. 
7 Pekelharing, " Untersuch. ti. d. Fibrin-ferment," Amsterdam, 1892; Halliburton, 
Journ. Physiol., Cambridge and London, 1S95, vol. xviii. p. 312. 
s Pekelharing. Cf. , however, C. J. Martin, "Venom of Australian Black Snake," 
pp. 36-10, Journ. and Proc. Roy. Soc. New South Wales, Sydney, July 3, 1895. 
