952 PHYSIOLOGY 



the mixture added to the oxalate plasma the latter clots. The same 

 effect is produced if the precipitate plus calcium be added to a pure 

 solution of fibrinogen. We must conclude that the precipitate, though 

 itself not fibrin ferment, will give rise to fibrin ferment on treatment 

 with lime salts. It was therefore designated by Hammarsten ' pro- 

 thrombin,' and regarded as the precursor of thrombin. 



Thus far practically all workers on the subject are agreed. 

 Coagulation of the blood is due finally to the coagulation of thrombin 

 and fibrinogen. The fibrinogen is present as such in the circulating 

 plasma. Thrombin is not contained in the circulating blood, but is 

 produced from some precursor or precursors after the blood has been 

 shed. For the production of thrombin the presence of calcium salts 

 is necessary. Further research on the nature of the precursor pro- 

 thrombin has shown that the matter is not quite so simple as imagined 

 by Hammarsten. In the following account we shall adhere chiefly 

 to the account as given by Morawitz, reserving most of the criticisms 

 and limitations to be made to this theory for the historical sketch of 

 the theories of clotting at the end of this section. 



Oxalate plasma which has been separated from the precipitate of 

 prothrombin can be made to coagulate by the addition of extracts of 

 almost any animal tissues together with lime salts, and these there- 

 fore were supposed to contain prothrombin similar to that obtained 

 by cooling oxalate plasma. These extracts even on mixture with 

 calcium are, however, without effect on pure solutions of fibrinogen, 

 and moreover the precipitate produced by cold, if thoroughly washed 

 before treatment with lime salts, loses its power of evoking coagulation 

 in fibrinogen solutions. Prothrombin is therefore unable by itself, 

 even on addition of lime salts, to produce fibrin ferment, but needs 

 the co-operation of some other substance which is contained in oxalate 

 plasma and which generally adheres in sufficient quantities to the 

 precipitate produced by cooling. Three factors are therefore necessary 

 for the production of fibrin ferment : firstly, lime salts ; secondly, a 

 substance present in the precipitate of prothrombin as well as in most 

 animal tissues ; and thirdly, a substance present in solution in oxalate 

 plasma. These two latter substances have been designated by 

 Morawitz thrombokinase and thrombogen. Thrombokinase is con- 

 tained in tissues and also in the blood-platelets. It can be obtained 

 by extraction of the stroma of the red blood- corpuscles or of the 

 bodies of lymph-cells or leucocytes. Separation of the blood-platelets 

 by cooling in the form of the disc-like precipitation abolishes the 

 spontaneous coagulability of any form of plasma. The thrombogen 

 is contained in solution in oxalate plasma. It is therefore con- 

 cluded that when blood leaves the vessels there is a disintegration of 

 the blood-platelets with the liberation of thrombokinase. This acts 



