THE BLOOD 



least is present only in minute traces, but makes its appearance immediately 

 the blood is drawn. Its origin is therefore of peculiar interest. 



It has been claimed by some, notably Peckelharing, that thrombin 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 consider- 

 able quantity when blood is drawn under ordinary conditions. Its appearance 

 is due to at least three antecedent substances, prothrombin (thrombogen), 

 calcium, and thrombokinase. The sources of these substances and the 

 part taken by each in the process of coagulation are as follows: If blood 

 be drawn, centrifugalized, and the blood plates separated, freed from plasma, 

 and suspended in water, their solution will cause the formation of fibrin 

 from fibrinogen in the presence of calcium and thrombokinase. The blood 

 platelets are, therefore, the source of the thrombogen. The thrombokinase 

 can be traced to its origin in the tissue cells and the formed elements of the 

 blood, especially the leucocytes. If blood is drawn from the vessels with 

 due precautions 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 cen- 

 trifuge 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. A solution of extract of washed 

 white corpuscles acts to increase the rapidity of coagulation. If precautions 

 are taken to draw the blood in such a manner as to remove 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 can be removed by precipitation with oxalate solution, or by fluorides. 

 Oxalate plasma contains both prothrombin and thrombokinase, and when- 

 ever calcium chloride is added to slight excess coagulation takes place. In 

 fluoride plasma one must add both calcium and thrombokinase as that sub- 

 stance seems to prevent the setting free of thrombokinase from the corpuscles. 

 The prothrombin is not interfered with by fluoride. 



In a word, one may say that the coagulation of the blood takes place 

 because of the formation of fibrin from fibrinogen by the action of thrombin. 

 The fibrinogen is constantly present in the plasma. The thrombin is formed 

 by the interaction of three substances, prothrombin, thrombokinase, and cal- 

 cium. The prothrombin arises chiefly from the disintegration of the blood 

 platelets when the blood leaves the blood-vessels. The thrombokinase 

 originates in tissue cells of the blood and of the organs of the body in general. 

 The calcium is present in the blood plasma at all times. 



Conditions Affecting Coagulation. From the preceding discussion 

 it is evident that the rapidity of the coagulation of the blood will be influenced 

 by anything that will influence the formation of the fibrin factors or their 

 interaction. The most important influences are the following: 



