38 A MANUAL OF PHYSIOLOGY 



(thrombin) is rapidly formed by the action of thrombokinase, 

 liberated from the leucocytes, the blood-plates, and possibly to some 

 extent from the erythrocytes, upon thrombogen, already present in 

 the circulating plasma. Further and this is of great practical 

 importance since no vessel is opened under ordinary circumstances 

 except through a wound in the overlying structures, the cut tissues 

 supply a store of thrombokinase at the point where it is required to 

 aid in the stanching of the wound. Calcium is essential to the reac- 

 tion by which thrombogen and thrombokinase form fibrin- ferment, 

 but is not necessary for that action of fibrin-ferment on fibrinogen 

 by which fibrin is produced (Practical Exercises, pp. 55-57). 



Both thrombogen and thrombokinase have close relations with 

 a substance or substances belonging to the group of nucleo- 

 proteins. If they are not actually nucleo-proteins, they cling 

 to them with such tenacity that it is not easy by ordinary means 

 to separate them. Thus nucleo-protein can be obtained from 

 solutions of fibrin-ferment, and, by appropriate treatment and 

 in the presence of proper conditions, solutions of nucleo-protein 

 can be made to influence coagulation in the way characteristic 

 of fibrin-ferment. Nucleo-proteins are contained in the nuclei 

 and protoplasm of cells, and have been prepared from the 

 thymus, testis, kidney, lymphatic glands, and other organs, by 

 precipitating their watery extracts with dilute acetic acid (Wool- 

 dridge), or by extracting with sodium chloride and then pre- 

 cipitating with excess of water (Halliburton). The precipitated 

 nucleo-protein can be dissolved in dilute sodium carbonate 

 solution. When it is injected slowly or in small amount into 

 the veins of an animal, it abolishes for a time the power of coagula- 

 tion of the blood ; and when this ' negative phase,' as it is called, 

 has been once established, even a very large and rapid injection 

 produces no further effect, possibly because an antibody which 

 neutralizes the action of thrombokinase has been produced. 

 If, however, a considerable quantity of the solution has been 

 injected at the first, the result is very different : extensive 

 intravascular clotting instantly ensues ; the animal dies in a few 

 minutes ; and the right side of the heart, the venae cavse, the 

 portal vein, and perhaps the pulmonary arteries, may be found 

 choked with thrombi. Here the injected thrombokinase is 

 responsible for the clotting, thrombogen and calcium being 

 already present. Curiously enough, intravascular coagulation 

 fails to be produced in a certain proportion of cases when albino 

 animals are injected with nucleo-protein from pigmented animals, 

 while there is no absolute failure of coagulation when albinos 

 are injected with nucleo-protein from albinos, and no failure 

 when pigmented animals are injected with material either 

 from other pigmented animals or from albinos. Intravascular 



