THE CA USE OF THE CO A G ULA TION OF BLOOD. 179 
fibrinogen, nucleo - proteid 'prothrombin), and lime, and it would 
appear probable from Pekelharing's researches that the two latter act 
in combination, and in fad nl the body which was termed by 
Schmidt the Qbrin ferment (thrombin). The reason why in the healthy 
living vessels the blood il<r> not coagulate, is, in all probability, thai the 
nucleo-proteid and lime have nol entered into the necessary combina- 
tion or interaction which enables them to act as a ferment upon the 
fibrinogen. 1 
Of the three factors above mentioned, it is certain that fibrinogen and 
lime arc both present in the plasma of circulating blood, and the problem 
therefore resolves itself into the question whether nucleo-proteid is 
present or not, or whether, if present, it is in a different condition from 
that necessary to promote fibrin formation. We may consider the latter 
question first, and in doing so it will be convenient to assume, as 
the experiments of Pekelharing seem to have proved, that the fibrin 
ferment of Schmidt is a product of the interaction of nucleo-proteid with 
lime. This conclusion of Pekelharing's has, in fact, been confirmed by 
the researches of Hammarsten, who has shown that the nucleo-proteid 
(or prothrombin ) which is obtainable from plasma is inactive as a ferment, 
except in the presence of or after it has been exposed to the action of 
soluble lime salts. It is not, however, equally clear that the fibrin 
ferment is a compound of the prothrombin with lime, as Pekelharing 
supposed it to be. 
Is fibrin ferment present in the plasma of circulating blood ? As is 
well known, Schmidt's fibrin ferment is ordinarily obtained from clotted 
blood or from serum, and the ferment-like substance used by A. 
Buchanan was also obtained by him from hi 1 clot, anil especially 
from buffy coat, Le. the portion containing most white corpuscles. 
Schmidt found that if blood were drawn from the vessels direct into 
alcohol, no ferment could be obtained from it. 2 He came, therefore, to 
the conclusion that the blood does not coagulate in the living vessels 
owing to the absence of fibrin ferment, and that this is only formed in- 
set free when the blood is drawn. Since fibrin ferment could be obtained 
in greatest abundance from the layer of the clot where leucocytes are 
most abundant, and from other tissues and organs rich in similar cells, it 
appeared probable that it is derived in drawn blood from the white 
corpuscles, and, as Schmidt believed, from their disintegration. Such 
disintegration of leucocytes was in fact described by Schmidt in drawn 
blood, hut the observation has not been generally confirmed. It is not, 
however, necessary to suppose disintegration of the corpuscles, for they 
may shed out the ferment without actually undergoing disintegration. 
Now, conditions which render the blood incoagulable, such as injections 
of " peptones," of snake venom, and nucleo-proteids in small amount, 
greatly diminish the number of leucocytes in the blood. This they do, 
however, not by causing the solution and disintegration of the corpuscles, 
1 Hammarsten. Ztschr. f. physiol. Ohem., Strassburg, 1896, Bd. xxii. We may dismiss 
the hypothesis of Astley Cooper (Thackrah, "An Essay on the Cause of the Coagulation 
of the Blood,"" Med.-Chir. Rev., London, 1807, p. 191), which was revived by Briicke, 
{Brit, and For. Med.-Chir. Rev., London, 1857, and Virchow's Archiv, 1857, Bd. xii.), that 
the living vascular walls exercise by their presence a restraining action upon coagulation, 
as having been sufficiently disproved by Lister ("On the Coagulation ' of the Blood," 
Proc. Roy. Soe. London, 1S63),_ 
- Subsequent researches conducted in his laboratory have shown that a very small 
amount is obtainable even under these conditions. 
