NATURE 



\_August 2, 1888 



enters into the condition of a heat coagulum at about 50 C. 

 The most abundant globulin is, however, one which resembles 

 serum globulin in its heat coagulation temperature (75 C), and 

 in the way in which it is precipitated by saturation with salts, or 

 by dialyzing out the salts from its solutions. 



The term serum globulin is hardly applicable to a proteid ex- 

 isting in lymph cells ; hence it is necessary to multiply terms, 

 and to designate this globulin by a new name, viz. cell globulin. 

 It has, moreover, certain characteristic properties which will be 

 fully dealt with later on. 



The Albumin resembles serum albumin in its properties. It 

 coagulates at 73° C. It is present in very small quantities. It 

 may be provisionally termed cell albumin. 



Having thus recognized the various proteids that occur in the 

 cells of lymphatic glands, my next endeavour was to ascertain 

 what action, if any, these exerted on the coagulation of the 

 blood. My experiments in this direction have been mostly per- 

 formed with salted plasma. The blood is received into an 

 approximately equal volume of saturated sodium sulphate solu- 

 tion. By this means coagulation is prevented, and the corpuscles 

 settle. On subsequently removing the supernatant salted 

 plasma, and diluting it with four or five times its bulk of water, 

 coagulation occurs after the lapse usually of several hours ; but 

 if, instead of water, a solution of fibrin ferment be used, 

 coagulation occurs in a few minutes. 



I first tried to prepare fibrin ferment from the lymphatic 

 glands ; these were freed from blood, chopped small, and placed 

 under absolute alcohol for some months ; they were then dried 

 over sulphuric acid, powdered, and the dry powder extracted 

 with water. The water was found to contain the fibrin ferment. 

 It hastened very considerably the coagulation of salted plasma. 

 This activity was destroyed at a temperature between 74 C. and 

 8o° C. The watery extract gave, moreover, the xanthoproteic 

 reaction ; it contained also some sodium chloride and phosphates 

 which it had dissolved out of the dried glands. 



A watery or saline extract of fresh glands also had very con- 

 siderable clotting powers ; that is to say, the addition of a few 

 drops of such an extract caused diluted salted plasma to clot in a 

 few minutes, which otherwise did not clot until after the lapse 

 of 12-24 hours. The activity of this extract was not altered 

 by heating to 70 ; it was therefore independent of the nucleo- 

 albumin which is disintegrated at about 50 C, or of the globulin 

 which coagulates at that temperature. Its activity was de- 

 stroyed, however, if heated above 75 C. These facts show that 

 the extracts of both dried and fresh glands contain a substance 

 which has the same properties as fibrin ferment, and which, 

 moreover, is rendered inactive at the temperature at which 

 fibrin ferment, as ordinarily prepared from serum, loses its 

 activity. 



The next question which I investigated was whether the 

 ferment action was dependent upon, or independent of, the 

 presence of the proteids of the cells. An extract of the cells 

 was made with sodium sulphate solution, and saturated with 

 ammonium sulphate ; the precipitate of the proteids so pro- 

 duced was filtered off ; the proteid-free filtrate dialyzed till free 

 from excess of salt, and it was then found to have no power of 

 hastening coagulation. The precipitate which contained all the 

 proteids was washed by saturated solution of ammonium 

 sulphate, and redissolved by adding distilled water ; this solution 

 hastened the coagulation of salted plasma very considerably. 

 This experiment showed either that the ferment was identical 

 with or precipitated with the proteids in the extract. It was, 

 moreover, destroyed at a temperature at which these proteids 

 were coagulated, viz. about 75 C. ; there are, however, in the 

 solution two proteids which are coagulated at about this tem- 

 perature, viz. the cell globulin and the cell albumin. The 

 globulin and the albumin were then separated from one another, 

 and it was fuinl that the globulin and not the albumin had the 

 properties of fibrin ferment. 



After I had performed the experiments just related, the 

 question naturally arose, Is this cell globulin the same thing as 

 what has been termed fibrin ferment when prepared from serum ? 

 From the experiments which were performed in order to elucidate 

 this question the following conclusions were drawn : — 



(1) Lymph cells yield as one of their disintegration products 

 a globulin which may be called cell globulin. This has the 

 properties that have hitherto been ascribed to fibrin ferment. 



(2) Fibrin ferment as extracted from the dried alcoholic pre- 

 cipitate of blood serum is found on concentration to be a globulin 

 with the properties of cell globulin. 



(3) The fibrin ferment as extracted by saline solutions from 

 "washed blood clot " is a globulin which is also identical with 

 cell globulin. 



(4) Serum globulin as prepared from hydrocele fluid has no 

 fibrinoplastic properties. It may perhaps be better termed 

 plasma globulin. 



(5) Serum globulin as prepared from serum has marked fibrino- 

 plastic properties. This is because it consists of plasma globulin, 

 and celi globulin derived from the disintegration of white blood 

 corpuscles, which are in origin lymph cells. 



(6) The cause of coagulation of the blood is primarily the 

 disintegration of the white blood corpuscles ; they liberate cell 

 globulin, which acts as a ferment converting fibrinogen into 

 fibrin. It does not apparently become a constituent part of the 

 fibrin formed. 



This confirmation and amplification of Hammarsten's views 

 concerning the cause of the coagulation of the blood is in direct 

 opposition to the theories of Wooldridge, which may be stated 

 as follows : — The coagulation of the blood is a phenomenon 

 essentially similar to crystallization ; in the plasma there are 

 three constituents concerned in coagulation, A, B, and C 

 fibrinogen. A and B fibrinogen are compounds of lecithin and 

 proteid, and fibrin results from the transference of the lecithin 

 from A fibrinogen to B fibrinogen. C fibrinogen is what has 

 hitherto been called fibrinogen ; A fibrinogen is a substance 

 which may be precipitated by cooling "peptone plasma," and on 

 the removal of this substance coagulation occurs with great diffi- 

 culty. The precipitate produced by cold consists of rounded 

 bodies resembling the blood-plates in appearance. He further 

 found that other compounds of lecithin and proteid, to which he 

 has extended the name of fibrinogen, exist in the thymus and 

 other organs, in the fluid of lymph glands, and in the stromata 

 of red corpuscles ; these substances may be extracted from the 

 organs by water, and precipitated from the aqueous extract by 

 acetic acid, and on redissolving this in a saline solution, and 

 injecting it into the circulation of a living animal, intravascular 

 clotting occurs which results in the death of the animal. This 

 form of fibrinogen (?) that acts thus he looks upon as the pre- 

 cursor of A fibrinogen. From these points of view the fibrin 

 ferment and the white corpuscles are looked upon as of secondary 

 import in causing coagulation, though it is admitted that fibrin 

 ferment converts C fibrinogen into fibrin. 



The Influence of Lecithin in the Coagulation of the Blood. — 

 Lecithin hastens the coagulation of blood -plasma, which has 

 been prevented from clotting by the injection into the cir- 

 culation of a certain quantity of commercial peptone ; but 

 peptone plasma, as I shall show more fully in the next section, 

 differs so much from normal plasma, that it is impossible to draw 

 correct conclusions from experiments performed with it, unless 

 they be supported by confirmatory evidence on solutions of 

 fibrinogen and pure plasma, such as one obtains from a vein, or 

 from the pericardial sac, and lecithin does not cause coagulation 

 in such cases. 



The supposition that "fibrinogen A" acts by giving up its 

 lecithin to "fibrinogen B' : to form fibrin, seems, therefore, to 

 be a pure assumption, and is unsupported by analytical evidence. 

 Cell globulin contains no phosphorus, and can therefore contain 

 no lecithin. 



The Precipitate produced by cooling Peptone Plasma. — The chief 

 point I wish to urge is that this precipitate is obtained on 

 cooling peptone plasma only, and from no other form of plasma. 

 I have repeatedly attempted to obtain such a precipitate by 

 cooling to o° C. pure plasma from the veins of the horse, salted 

 plasma, hydrocele fluid, and pericardial fluid, but in all cases 

 with a negative result. It therefore occurs in peptone plasma 

 alone ; and that it is due to the peptone is supported by the fact 

 that if one takes an aqueous solution of " Witte's peptone" and 

 cools it too°C, a precipitate is formed consisting of rounded 

 granules very similar to blood-tablets. This precipitate more- 

 over consists of hetero-albumose. (Witte's peptone contains a 

 large admixture of albumose.) That peptone blood does differ 

 in one other important particular from normal blood, viz. in 

 the heat coagulation temperatures of its proteids, was shown by 

 Wooldridge himself. It is on these grounds, then, that I hold 

 we cannot regard peptone plasma as being at all comparable to 

 normal plasma. 



Intravascular Coagulation. — No doubt the crude and impure 

 substance introduced into the veins produces intrava cular dot- 

 ting ; but I must protest against the extension of the name 

 fibrinogen to such substances. It seems to me it would be just as 



