THE COAGULATION OF THE BLOOD 951 



Moreover the action of thrombin on fibrinogen solutions is almost 

 independent of temperature, occurring practically as rapidly at 17 C. 

 as at 40 C. It has been found that there is only a slight increase in 

 the rate of action of snake venom on fibrinogen solutions on warming 

 from 20 to 40 C. Rettger therefore regards fibrin as formed by the 

 union of thrombin and fibrinogen. This union is apparently very 

 unstable. If fibrin be extracted with a 3 per cent, salt solution for 

 some time, part of it goes into solution, and the solution is found to 

 contain thrombin. In the same way the thrombin may be re-extracted 

 from the fibrin if the latter be allowed to putrefy. 



From all the different kinds of plasma which have been enumerated 

 above the purified fibrinogen can be obtained by the use of sodium 

 chloride, and in every case can be made to clot by the addition of 

 serum or of a solution of thrombin. The last change in the act of 

 clotting is therefore the change from fibrinogen to fibrin, and this 

 event is brought about by the intervention of thrombin. It cannot 

 be at this stage of the process that the calcium salts exercise their 

 influence, since ' fibrin ferment ' or thrombin will cause the coagulation 

 of fibrinogen in the total absence of soluble calcium salts and even 

 in the presence of a slight amount of ammonium oxalate. Moreover 

 Hammarsten has shown that the calcium content of fibrin is no greater 

 than that of the fibrinogen from which it is formed. 



The fact that a solution of pure fibrinogen is made to clot by 

 thrombin and by this alone renders such a solution an excellent 

 reagent for the presence of the * ferment.' By this means we can show 

 that thrombin is absent in circulating blood. If blood be received 

 direct from the vessels into absolute alcohol and the precipitate, 

 after coagulation by alcohol, be extracted by water, the extract is 

 found to contain no trace of ferment. The same statement applies 

 to fresh oxalate plasma. If, however, oxalate plasma be made to 

 clot by the addition of calcium salts, the serum squeezed from the 

 clot is found to contain thrombin. In the process of coagulation there- 

 fore not only is there a conversion of fibrinogen to fibrin, but there is an 

 actual formation of the agent which is responsible for this change, 

 namely, thrombin or fibrin ferment. Our next step therefore must be 

 to inquire into the precursors of the thrombin and the conditions of 

 its formation. 



If oxalate plasma be cooled to C. for two or three days a scanty 

 granular precipitate is produced. This can be centrifuged off or 

 separated by filtration through several thicknesses of paper. It is 

 then found that the remaining plasma can no longer be made to 

 coagulate by the addition of lime salts, although it still contains 

 fibrinogen, which is converted into fibrin on the addition of thrombin. 

 If the precipitate be collected and treated with calcium chloride and 



