844 PHYSIOLOGY 



These extracts even on mixture with calcium are, however, without effect on 

 pure solutions of fibrogen, 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 : 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 thrombokinase and 

 thrombogen. Thrombokinase 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 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 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 obtained from 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 



