

THE COAGULATION OF THE BLOOD 891 



the addition of dilute acetic acid) and thrombogen, as well as a fairly strong 

 solution of thrombin. Thrombin however 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 Kettger the disappearance of throm- 

 bin from serum is due to its combination 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 

 withstand even 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 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 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 interaction of the fibrin factors but actually slowly 

 precipitates the thrombokinase, so that if time be allowed for this precipitation to be 

 complete the remaining plasma contains only fibrinogen. 



SODIUM FLUORIDE PLASMA might be expected to act like oxalate plasma since sodium 

 fluoride is a precipitant of lime salts. This salt has however the additional property 

 of causing a certain amount of fixation of the formed elements of the blood as well as 

 of the blood platelets. If it be thoroughly centrifuged so that the plasma is obtained 

 free from these constituents, it will no longer clot with lime salts * nor even with lime 

 salts plus tissue extracts, but will clot, readily on addition of thrombin. Although it 

 still contains a certain amount of thrombogen, this is entangled and carried down in 

 the precipitate of calcium fluoride which is produced by the addition of lime salts, so 

 that the thrombokinase has nothing on which to exercise its effect. Sodium fluoride 

 plasma is therefore useful, like magnesium sulphate plasma, as a test for the presence 

 of thrombin. If water be added to the sodium fluoride blood, so as to destroy some of 

 the formed elements and liberate their constituents into the plasma, it is possible to 

 produce clotting by the simple addition of lime salts. 



1 According to Eettger this statement is incorrect. 



