THE COAGULATION OF THE BLOOD 849 



HIRUDIN PLASMA. The action of hirudin is that of an anti-thrombin. It apparently 

 combines with and neutralises fibrin ferment. Hirudin plasma can therefore be made 

 to clot by the addition of fibrin ferment in sufficiently large quantities to combine with 

 all the hirudin present and leave an excess over in the fluid. 



PEPTONE PLASMA presents many difficulties in the explanation of its behaviour. 

 Peptone itself has apparently no influence on the coagulation of the blood. Blood 

 received into peptone solution clots as rapidly as when received into salt solution. On 

 the other hand, if blood be received into peptone blood obtained by the injection of 

 large doses of peptone into the veins of another animal, the mixture does not clot, 

 showing that peptone blood contains some substance which inhibits the processes of 

 coagulation. This ' anticoagulin ' must be produced by the organism itself as a result 

 of the injection of peptone, and evidence has been brought forward by Delezenne and 

 others that the seat of formation of the anticoagulin is in the liver. Whether the anti- 

 substance partakes of the characters of an anti-thrombin or of an antikinase has not 

 yet been definitely ascertained. Peptone plasma can be made to clot by the addition 

 of tissue extracts even in small quantities. It still contains all the fibrin factors since 

 it will clot on simple dilution or on the passage of a current of carbon dioxide. It needs, 

 however, the addition of large quantities of fibrin ferment to bring about coagulation. 



THE TRANSUDATIONS 



The earlier work on the mechanism of coagulation was largely carried out 

 on the fluids obtained from the pericardial or pleural cavities or on hydrocele 

 fluid from the tunica vaginalis. These as a rule can be kept indefinitely 

 without clotting, but will clot readily on addition of a few drops of blood 

 or the washings of a blood-clot or fibrin ferment. They will not clot on the 

 addition of tissue extracts containing thrombokinase. Though they con- 

 tain leucocytes and even some red corpuscles, they are free from blood-plate- 

 lets. Their behaviour is readily explained by the assumption that they 

 contain fibrinogen, but are free from thrombokinase or thrombogen. In 

 order to produce coagulation it is therefore necessary to add two fibrin 

 factors, thrombokinase and thrombogen, as happens when we add blood, or 

 to treat them with fully formed thrombin or fibrin ferment. 



HISTORY OF THE COAGULATION QUESTION. It is not surprising that the 

 coagulation of the blood, with the antecedent changes which lead to the appearance 

 of thrombin and probably represent the successive stages in the disintegration of a fluid 

 labile protoplasmic molecule, i.e. the change from life to death of the plasma, should 

 have been the subject of a very large number of investigations, and that even at the 

 present time the interpretation of the salient facts presents many difficulties. Some 

 help may be given to the future clearing up of these difficulties by a study of the steps 

 by which our present standpoint has been arrived at. The universal practice of bleeding 

 as a therapeutic measure naturally afforded many opportunities to physicians for ob- 

 serving the processes of coagulation under diseased as well as healthy conditions. The 

 genera] result was, however, in most cases, a crop of ill-founded and uncritical theories, 

 and it is not till the time of Hewson (1772) that we meet with investigations of the 

 question carried out on modern lines with reference to observation and experiment 

 at each stage. We owe to Hewson the discovery that coagulation can be inhibited 

 indefinitely by the addition of neutral salts, such as sodium sulphate, and it was by a 

 study of such bloods that Hewson arrived at the conclusion that the formed elements 

 of the blood take no part in the production of the clot. Johannes Miiller in 1832 came 

 to the same conclusion from a study of frog's blood. This he diluted with sugar solution 

 and filtered through filter-paper. The large corpuscles were retained by the meshes 

 of the filter-paper and the clear fluid which came through slowly underwent coagulation. 



