THE COAGULATION OF THE BLOOD 851 



the occurrence of coagulation. According to Schmidt the plasma is itself derived from 

 the cells of the body, the fibrinogen being formed through the stages of paraglobulin 

 and cytoglobulin. The thrombin is derived from a precursor prothrombin under the 

 action of a zymoplastic substance also derived from the cells. In the presence of the 

 proper concentration of salts the thrombin acts upon fibrinogen to produce fibrin. His 

 views may be roughly expressed by the following schema given by Howell : 



Soluble fibrin - Salts = Fibrin 



Some important light was thrown on the subject by the researches of Wooldridge. 

 Working chiefly with peptone plasma, he showed in the first place that such plasma 

 contained all the factors necessary for the production of fibrin, and therefore that the 

 co-operation of leucocytes was not a necessary part of the process. Peptone plasma, 

 separated entirely from leucocytes and red corpuscles, could be made to clot by dilution, 

 by the passage of a stream of carbon dioxide or filtration through a clay cell. This 

 power of clotting without addition of any other substances depended on the presence in 

 the plasma of a substance called by Wooldridge ' A-fibrinogen,' which was thrown 

 down as a disc-like precipitate on cooling to C. On separating this precipitate, 

 which he regarded as equivalent to the blood-platelets, by means of the centrifuge, 

 the remaining plasma would only clot on the addition of extracts of tissues. Since 

 neither the original plasma nor the plasma after separation of the A-fibrinogen would 

 clot on the addition of fibrin ferment, Wooldridge thought that the fibrinogen of 

 Hammarsten was absent from such plasma, which only contained two fibrinogens, 

 A- and B-fibrinogen. Clotting therefore consisted essentially in an interaction between 

 A- and B-fibrinogen, and was inaugurated by the appearance of A-fibrinogen as a disc- 

 like precipitate. In this interaction he showed that ferment was produced, and the 

 weakest part of his theory was that it gave practically no office to the ferment pro- 

 duced during the first steps of the process imagined by him. The B-fibrinogen could 

 be thrown down by the action of dilute acid or of salt from the plasma after separation, 

 of the A-fibrinogen. After precipitation and re-solution two or three times it would 

 clot with fibrin ferment, and was coagulated at a temperature of 56 C., and was there- 

 fore the typical fibrinogen of Hammarsten. According to Wooldridge, therefore, 

 previous observers had been working, not with the fibrinogens of the plasma, but with 

 a fibrinogen altered by repeated precipitation and re -solution. One fact discovered 

 by him which at once attained universal recognition was the production of intra vascular 

 clotting by the injection of tissue extracts. These tissue extracts contained tissue 

 fibrinogens which he compared with A-fibrinogen. According to him clotting could 

 be inaugurated either by the action of A-fibrinogen on the B-fibrinogen, or by the 

 action of tissue fibrinogen on the B-fibrinogen of the plasma. In every case fibrin 

 ferment resulted and could therefore effect the conversion of any C-fibrinogen of 

 Hammarsten which might be present in the fibrin. It will be seeji that this theory of 

 Wooldridge presents a striking similarity to that which is generally accepted at the 

 present day. If we change the names of A-fibrinogen to thrombokinase, of B-fibrinogen 

 to thrombogen, we see that the only difference between Wooldridge's theory and that 

 of Morawitz is that the former ignored the importance of lime salts in the process and 



