158 THE BLOOD 



at once. The same effect is produced also by blood clot washed free of all 

 color with water. Such a clot contains fibrin and the remains of white cor- 

 puscles., so that one is inclined for many reasons to assume that the substance 

 which must be added to a solution of fibrinogen to make it clot, and which 

 has been designated the fibrin ferment or thrombin (A. Schmidt) comes 

 directly from the white blood corpuscles. It appears from several observations 

 that the white corpuscles themselves do not of necessity break down under 

 such circumstances, and Arthus has expressed the view that they give off 

 the fibrin ferment by a process of secretion. 



Coagulation cannot take place, as Arthus was the first to demonstrate, 

 without the presence of a soluble calcium salt. This is probably due to the 

 fact that fibrin ferment does not exist in the blood as such but in the form 

 of a mother substance, or zymogen, and is activated only in the presence of Ca 

 salts (Hammarsten, Pekelharing) . The calcium does not appear to be neces- 

 sary for the formation of fibrin, however, for a solution of fibrinogen coagu- 

 lates in the presence of thrombin even when the calcium salts are removed 

 by an oxalate. 



Coagulation is considerably accelerated by addition of extracts of all pos- 

 sible kinds of organs., and even by mere contact of the blood with the wound. 

 On this account it has been assumed that the contained nucleo-proteids might 

 represent precursors of the thrombin. On the contrary Arthus, Morawitz 

 and others believe that they only hasten the formation of the enzyme and 

 that the mother substance of the latter occurs exclusively in the blood. 



According to Morawitz the organ extracts effect the formation of the 

 proenzyme from a zymogen stage, thrombogen, whereupon thrombin arises 

 from the proenzyme under the influence of the calcium ions. 



The formation of thrombin is stopped immediately by sodium fluoride 

 and by addition of this salt in small quantities it is possible therefore to follow 

 the course of thrombin formation more closely. In this way it has been 

 shown that at the moment it flows from the vessel the blood contains no 

 thrombin at all, that the quantity of the enzyme increases quite slowly at 

 first, and that shortly before coagulation it undergoes a rapid increase. 

 Thrombin is formed for a time also after coagulation has taken place 

 (Arthus). 



When blood serum stands exposed to the air its enzyme gradually decreases 

 in quantity and disappears entirely after about six days. No more enzyme is 

 obtained after this time by addition of calcium salts. But by means of acids, 

 alkalies, alcohol, etc., one can demonstrate an effective fibrin ferment; there is 

 present therefore in the serum a body from which active fibrin ferment may be 

 formed. This body is absent from normal plasma and seems to make its appear- 

 ance for the first during coagulation. According to Fuld and Morawitz, it is 

 probable that this substance is thrombin itself, which had merely passed over 

 to an inactive state. 



The transformations brought about by enzymes in general appear to pro- 

 ceed in such a way that the substance acted on absorbs water and is subse- 

 quently split into two new substances. This is probably the case in fibrin 

 formation; the fibrinogen is split into insoluble fibrin which constitutes the 



