THE COAGULATION OF THE BLOOD 



Cells 



I 



Plasma 



961 



Cytoglobulin 



Paraglobulin 



I 

 Fibrinogen 



Zymoplastic 

 substance 



Prothrombin 



Thrombin 



Soluble fibrin - Salts = Fibrin 



Some important light was thrown on the subject by the researches of Wool- 

 dridge. 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 

 Hainmarsten 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 produced 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 therefore 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 dis- 

 covered by him which at once attained universal recognition was the production 

 of intravascular 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-fibri- 

 nogen on the B-fibrinogen, or by the action of tissue fibrinogen on the B-fibri- 

 nogen 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 seen 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 imagined that the interaction of thrombokinase and thrombogen resulted 

 in the direct production of fibrin as well as ferment, instead of recognising that 



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