122 THE BLOOD 



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. 



The sources of these substances and the part taken by each in the 

 process of coagulation are given by Morawitz. If blood be drawn, centri- 

 fugalized, 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 thrombin. The thrombin can be isolated in a 

 stable condition, and when its solutions are added to fibrinogen solutions 

 fibrin is formed. By Morawitz' view the appearance of thrombin in the 

 blood is due to the interaction of at least three antecedent substances. 

 These are, i, prothrombin (thrombogen), 2, calcium, and 3, thrombo- 

 kinase (cytozym). If the blood is drawn from vessels with due pre- 

 cautions, 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 activating substance or kinase to which 

 the name thrombokinase has been given by Morawitz. 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 made a 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: 



"Terrapin's blood taken carefully through an oiled cannula and put into 

 a perfectly clean beaker will remain fluid for days. The blood may be cen- 

 trifuged, and the clear supernatant plasma is then equally or more resistant 

 to spontaneous clotting. If, however, tissue extracts or pieces of tissue be 

 added, the coagulation is pronounced and immediate. The most apparent 

 explanation is that a thrombin or coagulin or kinase is present in the extract. 

 But this blood or plasma can be made to clot equally well and equally rapidly 

 in ways which preclude the presence of such a definite agent. If, for instance, 



