122 THE BLOOD 



The thrombin is the substance which reacts on the fibrinogen in the 

 processes of fibrin formation. It does not exist in the living blood 

 vessels, or at least is present only in minute quantities, but makes its 

 appearance immediately the blood is drawn. Its origin is therefore of 

 peculiar interest. 



Thrombin has not been chemically identified. But it is generally ad- 

 mitted that it is a calcium compound. At any rate, it is definitely proven 

 that calcium is a necessary element in the formation of the clot. 



The substance thrombin, fibrin ferment, quickly appears in considerable 

 quantity when blood is drawn under ordinary conditions. The sources of 

 these substances and the part taken by each in the process of coagulation 

 are as follows (Marowitz): If blood be drawn, centrifugalized, and the 

 leucocytes and blood plates separated from the plasma and suspended in 

 water, their solution will cause the formation of fibrin from fibrinogen in 

 the presence of calcium. The leucocytes and platelets are, therefore, the 

 source of thrombogen. The thrombin can be isolated in a stable condition, 

 and when its solutions are added to fibrinogen solutions fibrin is formed. 

 By Marowitz' view the appearance of thrombin in the blood is due to the 

 interaction of at least three antecedent substances. These are, i, pro- 

 thrombin (thrombogen), 2, calcium, and 3, thrombokinase (cytozym). If 

 the blood is drawn from vessels with due precautions, i.e., not to allow it to 

 come in contact with the cut vessel or other tissue, clotting is very much 

 delayed. The plasma if separated by the centrifuge will remain unclotted 

 for a long time as shown by Howell for the terrapin's plasma. This plasma 

 will quickly clot at any time if a few drops of tissue extract in salt solution be 

 added. When blood is drawn over the lacerated tissue of a wound it clots 

 more quickly. These observations have led to the assumption of an acti- 

 vating substance or kinase to which the name thrombokinase has been given. 

 It is assumed to have its origin in tissue cells and in the cells of the blood, 

 especially the leucocytes. 



If precautions are taken to draw the blood in such a manner as to re- 

 move the calcium from the plasma, no clot is formed. The calcium which 

 exists in solution in the plasma to the extent of 0.026 per cent, (measured 

 as calcium chloride) can be removed by precipitation with oxalate solution 

 or by the action of fluorides or citrates which bind the calcium so that it is 

 no longer available to the prothrombin. Such plasma contains fibrinogen, 

 prothrombin, and thrombokinase, and whenever calcium chloride is added 

 to excess, coagulation takes place. 



L. J. Rettger has recently, 1909, made an exhaustive re-examination 

 of the conditions for the clotting of blood. He questions the interpretation 

 of the facts on the basis of which the assumption of a kinase is made. 

 He says : ' ' After such prolonged irrigation, to remove every trace of blood or 

 serum, bits of the organ or tissue were macerated in 0.9 per cent, solution 



