THE CAUSE OF THE COAGULATION 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 fact represent the body which was termed by 

 Schmidt the fibrin ferment (thrombin). The reason why in the healthy 

 living vessels the blood does not coagulate, is, in all probability, that the 

 nucleo-proteid and lime have not 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 are 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 blood clot, and especially 

 from buffy coat, i.e. 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 or 

 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, but 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. Chem., 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.-CMr. Rev., London, 1807, p. 191), which was revived by Briicke, 

 (Srit. 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. Soc. London, 1863). 



2 Subsequent researches conducted in his laboratory have shown that a very small 

 amount is obtainable even under these conditions. 



