FIBRIN FORMATION 263 



anything more than the essential principles involved in the clot- 

 ting of the blood, as now understood, as an introduction to the 

 consideration of the same process as it occurs under pathologi- 

 cal conditions. In spite of innumerable investigations, our 

 knowledge of the actual participants and processes involved in 

 the formation of fibrin is in a very unsatisfactory and fragment- 

 ary state. Some facts seem well established, however, and we 

 have a general idea of the subject that may be applied with 

 advantage to the consideration of thrombosis. 



FIBRIN FORMATION 1 



Several different substances seem to be concerned in the formation of 

 fibrin, of which the first of importance is its antecedent, fibrinogen. 

 Fibrinogen is a simple proteid, related to the globulins, and differing 

 chiefly in its ready coagulability, not only by fibrin ferment, but also by 

 heat, salts, and other coagulating agencies. By itself, however, it shows 

 no tendency to coagulate spontaneously. According to Mathews, 2 

 fibrinogen is formed chiefly in the intestinal walls from the leucocytes. 

 Acted upon by the fibrin-ferment, it yields the characteristic insoluble 

 proteid, fibrin ; probably the change consists in a cleavage of the fibrino- 

 gen molecule into fibrin and a small amount of a soluble proteid. Fibrin 

 resembles in its insolubility the proteids coagulated by heat, alcohol, etc., 

 but when kept aseptically for some time, it becomes again dissolved ; this 

 process of fibrinolysis probably depends upon proteolytic enzymes which 

 fibrin, in common with other substances of similar physical nature, has 

 the property of dragging out of solution and holding firmly. Undoubt- 

 edly entangled leucocytes are also an important factor in the fibrin- 

 olysis. 3 



Theories of Fibrin Formation. The great problem is the nature 

 and the place and manner of origin of the fibrin-forming enzyme, 

 generally called fibrin-ferment (also p losmose and coaguliri). It has been 

 conclusively shown that the agent causing the formation of fibrin from 

 fibrinogen is a true enzyme, but, as with the other enzymes, it is not 

 known whether fibrin-ferment is a nucleoproteid (Pekelharing) or any 

 other sort of a proteid. The best known and most fundamental theory 

 of the origin and nature of fibrin-ferment is that of Alexander Schmidt, 

 which may be briefly described as follows: The ferment, Schmidt 

 believes, exists in the plasma in an inactive (prozyme or zymogeri) form, 

 which he calls prothrombin. Upon disintegration of the leucocytes there 

 is set free a substance, which, acting upon the prothrombin, converts it 

 into the active thrombin ; this activating agent Schmidt designates as 

 the zymoplastic substance. With various modifications this theory stands 



1 For literature and full discussion see Hammarsten's Physiological Chemis- 

 try ; more recent literature by Morawitz, Ergebnisse der Physiol., Abt. 1, 1904 

 (4), 307; and Blum, Cent, f" Path., 1904 (15), 385. Re'sum^ of recent work 

 by Leo Loeb, Medical News, 1905 (86), 577. 



2 Amer. Jour. Physiol., 1899 (3), 53; a different view is held by Doyon, 

 Morel and Kareff (Jour.de physiol., 1906 (8), 783) 



3 See Morawitz, loc. cit. ; also Rulot, Arch, internat. d. Physiol., 1904 (1), 

 152. 



