336 THE BLOOD. 



appears as insoluble fibrin. At present this view has lost support 

 through the fact that fibrinogen solutions can be prepared from which 

 no fibrinoglobulin is split off either during clotting or upon heat 

 coagulation. Nevertheless it is possible that the process is a hydro- 

 lytic one and we may imagine, as Abderhalden suggests, that 

 fibrinogen is composed of several fibrin molecules which are set 

 free as the result of the action of the fibrin ferment, with a coincident 

 taking up of water. 



The fibrin-ferment, according to our present concept, does not 

 exist in the blood as such, but as an inactive zymogen prothrombin 

 which must first be activated before it can manifest its activity. 

 It was formerly supposed that the transformation of the zymogen 

 into the enzyme was brought about by soluble calcium salts, as it 

 could be shown that coagulation only occurs when such are present. 

 There is evidence, however, to show that the activation occurs 

 through a special kinase (cytozyme, zymoplastic substance), as in 

 the case of trypsin, which is now generally spoken of as thrombo- 

 kinase, and which itself must first be activated ; this is probably 

 brought about through the calcium salts. 



As regards the origin of the kinase we know that it is derived 

 from the tissues in general. Under suitable conditions (blood of 

 birds and terrapins) no coagulation of the blood thus occurs if precau- 

 tions are taken to prevent its coming in contact with the wound 

 and if the corpuscles are then at once thrown down by centrifuga- 

 tion (Howell, Delezenne). The zymogen, on the other hand, is 

 supposedly furnished by the blood-platelets and leucocytes. It is 

 known, however, that other cells of the body also contain substances 

 which can induce or, at least, hasten coagulation. 



The ferment nature of the thrombin is shown by the facts that a 

 very small amount is necessary to effect the coagulation of a very 

 large amount of blood and that no coagulation occurs on heating the 

 ferment to 100 C. Its optimum temperature lies at 37 C. 



Of interest in this connection is the fact that the ferment (accord- 

 ing to Schmidt) cannot be kept in solution and retain its activity. 

 It becomes inactive, but can under certain conditions be activated 

 again by the addition of an alkali, to become inactive again on 

 neutralization, etc. Of the chemical nature of the ferment nothing 

 is known. It is generally regarded as a nucleoproteid (Pekel- 

 haring) and is said to yield a nuclein on peptic digestion. 



Isolation. The isolation of impure fibrin-ferment is most con- 

 veniently accomplished in the following manner: Taking the serum 

 of the ox, the globulins are first precipitated by saturation with 

 magnesium sulphate. The filtrate is then diluted with water, and 

 treated while stirring with a very dilute solution of sodium hydrate 

 until an abundant and flocculent precipitation of magnesium hydrox- 

 ide has been brought about. This precipitate, which contains a 

 large proportion of the ferment, is washed with water, pressed 

 between filter-paper, and dissolved in water by neutralizing the 



