THE COAGULATION OF THE BLOOD 959 



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 contain leucocytes and 

 even some red corpuscles, they are free from blood-platelets. 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 appear- 

 ance 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 observing the processes 

 of coagulation under diseased as well as healthy conditions. The general 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 frogs' 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. The beginning of our 

 modern ideas on the subject must be ascribed to Buchanan, though many of 

 the facts discovered by this observer escaped general recognition and were 

 later re-discovered by Alexander Schmidt. Buchanan worked chiefly on hydro- 

 cele fluid and showed that this could be made to yield fibrin by treatment with 

 fresh blood or by adding it to the washings of a blood-clot. He compares the 

 action of the latter to that of rennet on the protein of milk. His experiments 

 showed that ' fibrin has not the least tendency to deposit itself spontaneously 

 in the form of a coagulum, that, like albumin and casein, fibrin often coagulates 

 under the influence of suitable reagents, and that the blood, like most other 

 liquids of the body which appear to coagulate spontaneously, only do so in 

 consequence of their containing at once fibrin and substances capable of reacting 

 upon it and so occasioning coagulation.' He held therefore that the coagulation 

 of the blood is due to the conversion of a soluble constituent of the liquor 

 sanguinis into fibrin by an action exerted probably by the colourless corpuscles 

 and comparable to the action which rennet exerts in effecting the coagulation 

 of milk. Furthermore, the liquid which accumulates in certain serous sacs 

 may be made to yield a coagulum of fibrin when subjected to the action of liquids 



