THE COAGULATION OF THE BLOOD 887 



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 Hme 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 : first, 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 thrombo- 

 kinase and thrombogen. Thromboldnase is contained 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 and filtration abolishes 

 the spontaneous coagulability of any form of plasma. The thrombogen 

 is contained in solution in oxalate plasma. It is therefore concluded that 

 when blood leaves the vessels there is a disintegration of the blood platelets 

 with the liberation of thrombokinase. This acts upon thrombogen in the 

 presence of lime salts and produces thrombin. By the intermediation of 

 the thrombin the fibrinogen also present in solution in the plasma is con- 

 verted into fibrin. The changes occurring in shed blood and resulting in the 

 production of a clot are therefore mainly concerned with the production of 

 the fibrin ferment. This view of the essential characters of coagula- 

 tion is borne out by observations on other forms of plasma, especially of 

 plasma of birds' blood. This when obtained with scrupulous cleanliness 

 so as to avoid any contamination with dust or with the tissues remains 

 permanently uncoagulable. In the plasma got by centrifuging the blood 

 no blood platelets are to be seen, and no precipitate is produced by 

 exposure to a temperature of C. We may say therefore that blood 

 platelets with their contained thrombokinase are absent from birds' blood, 

 and with them the property of spontaneous coagulability. It is also 

 free from fibrin ferment, but contains thrombogen as well as soluble lime 

 . salts. It is only necessary therefore to add thrombokinase in the shape 

 of a watery extract of any tissue in order to cause the appearance of fibrin 

 ferment and the conversion of the fibrinogen already present in the plasma 

 into fibrin. 



In every case the initiation of the act of clotting would seem to depend 

 on the setting free of thrombokinase in the plasma. In mammalian blood, 

 although thrombokinase can be derived from red or white corpuscles, we 

 have no reason to believe that there is any appreciable disintegration of these 

 formed elements when the blood leaves the vessels. In oxalate blood 

 leucocytes can be seen alive and exercising amoeboid movements two or three 

 days after the blood has left the vessels, and although certain observers have 

 assumed the presence of explosive corpuscles which break up directly the 



