172 ESSENTIALS OF PHYSIOLOGY. 



Thrombogen, lime salts, and fibrinogen exist normally in blood. 

 When blood is shed, thrombokinase, derived from blood platelets or 

 from the tissues, brings about the combination of thrombogen and lime 

 salts to form thrombin ; thrombin then combines quantitatively with 

 fibrinogen to form fibrin. 



The Nature of Thrombin. For many years thrombin was believed 

 to belong to the group of ferments, but it has been shown (1) that it is 

 not destroyed by boiling, and (2) that the amount of fibrin formed is 

 in proportion to the amount of thrombin present. (1) Thrombin in 

 watery solution is not affected by boiling, but thrombin contained in 

 serum is inactivated by boiling. The inactivated substance in the 

 latter case, however, is reactivated by the addition of alkali. The 

 destruction of a ferment, on the other hand, at a temperature of 100 C 

 is one of its most characteristic features. (2) It is also characteristic 

 of a ferment that, if the products of its activity be removed, it will in 

 time act upon all the substrate which is present. Thrombin, on the 

 other hand, is used up in the formation of fibrin, so that if there is 

 an excess of fibrinogen the surplus remains unchanged, unless fresh 

 thrombin is added. 



If serum is allowed to stand for two or three days, the thrombin 

 contained in it disappears, being converted into a substance which has 

 been called metathrombin, and which can be reactivated by the addition 

 of either acids or alkalies, with subsequent neutralisation, or by the 

 occurrence of putrefaction. The same agencies, that is acids, alkalies, 

 or putrefaction, will break up fibrin, yielding thrombin. 



The fact that blood does not clot in the vessels must be due to one 

 of two things : either an essential factor for coagulation is not present, 

 or clotting is prevented by some agent which inhibits the process. 

 With regard to the former possibility, fibrinogen exists in normal 

 blood, calcium salts are undoubtedly present, and thrombogen must be 

 a constituent of the blood in some form. If it be accepted that 

 platelets are only formed when blood comes into contact with foreign 

 matter, it would appear that the immediate precursor of thrombokinase 

 is not in existence in the circulating blood. This has already been 

 shown to be the case in birds, the blood of which contains no platelets. 

 There is, therefore, good ground for believing that the circulating blood 

 contains little or no thrombokinase. As regards the second possibility, 

 evidence has been brought forward by some observers to show that a 

 substance, anticoagulin or antithrombin, is a normal constituent of blood, 

 and that it is formed in the liver. It is stated, for example, that the 

 injection of thrombokinase or of thrombin into a blood-vessel results in 

 the production of such an antibody, so that the blood becomes deficient 



