THE COAGULATION OF THE BLOOD 957 



bogen, as well as a fairly strong solution of thrombin. Thrombin, how- 

 ever, rapidly disappears from serum, so that a blood-serum which has 

 been kept for two or three days may be almost free from fibrin ferment. 

 Such a serum can be reactivated by the addition of small traces either 

 of acid or alkali. It has been suggested that the thrombin undergoes 

 a modification into an inactive form which is called metathrombin. 

 This substance has no relation to the precursors of fibrin ferment 

 which we have already considered. It is unaltered by lime salts or 

 by the addition of thrombokinase, but can be reconverted into 

 thrombin by means of acids or alkalies. According to Rettger 

 the disappearance of thrombin from serum is due to its combi- 

 nation with some of the proteins of the serum. This combination, 

 like that of thrombin with fibrinogen to form fibrin, is unstable 

 and can be broken up by the action of alkalies, acids, or even 

 of putrefaction. Thrombin itself seems to be extremely stable and 

 will even withstand the temperature of boiling water for a short 

 time. If solutions containing thrombin be evaporated to dryness the 

 dry residue can be heated to 135 C. without destruction of the 

 thrombin. 



We are now in a position to see how far the theory of coagulation 

 which we have evolved from a study of two forms of plasma will 

 serve to explain the behaviour of the many other kinds of plasma 

 which have been the subject of investigation. 



COOLED PLASMA contains the thrombokinase in the form of blood- 

 platelets or a disc-like precipitate. This precipitate can be separated 

 by centrifuging at a low temperature or by filtration. The remaining 

 plasma contains only thrombogen, lime salts, and fibrinogen, and 

 can be made to clot by the addition of tissue extracts or of fibrin 

 ferment, but will not clot on warming. 



In SODIUM SULPHATE PLASMA the interaction of the fibrin factors 

 is merely impeded by the excess of salt. All are still present, and it 

 is therefore sufficient merely to dilute the plasma in order to produce 

 clotting. 



MAGNESIUM SULPHATE PLASMA behaves somewhat differently. If 

 the blood be received directly into magnesium sulphate solution and 

 the mixture centrifuged while still warm, a clear magnesium sulphate 

 plasma is obtained which will clot on simple dilution. If the blood be 

 left for twenty-four hours before centrifuging, the plasma will not clot 

 on dilution nor on the addition of tissue extracts. It contains 

 fibrinogen only and is therefore an excellent reagent for the presence 

 of fibrin ferment. Magnesium sulphate not only hinders the inter- 

 action of the fibrin factors but actually slowly precipitates the thrombo- 

 kinase, so that if time be allowed for this precipitation to be complete 

 the remaining plasma contains only fibrinogen. 



