COAGULATION 35 



serum, too, which contains abundance of serum-globulin, but no 

 fibrinogen, will not coagulate. 



So far, then, we have reached the conclusion that fibrin is formed 

 by a change in a substance, fibrinogen, which can be obtained by 

 certain methods from blood-plasma. It may be added that there 

 is evidence that fibrinogen exists as such in the circulating blood; 

 for if unclotted blood be suddenly heated to about 56 C., the tem- 

 perature of heat-coagulation of fibrinogen, the blood for ever loses 

 its power of clotting. The liver seems to be an important place of 

 origin of fibrinogen, which may also be formed in the bone-marrow. 

 That the liver is intimately concerned in the production of fibrinogen 

 is indicated by a number of facts. In phosphorus poisoning, and 

 notably in poisoning by chloroform, which causes necrosis, especially 

 of the central portions of the hepatic lobules, the amount of 

 fibrinogen in the blood is quickly diminished. The diminution is 

 proportional to the extent of the injury to the liver, and the blood 

 loses more or less completely its power of clotting. If the injury 

 is repaired, the fibrinogen is rapidly regenerated (Whipple). If the 

 blood is allowed to circulate for a time in the head and thorax of 

 an animal without passing into the rest of the animal's body, it 

 becomes incoagulable, and the fibrinogen is found to be markedly 

 deficient in amount. When the blood of an animal is defibrinated 

 by whipping, and reinjected, regeneration of the fibrinogen does 

 not occur if the liver has been eliminated, whereas it takes place 

 rapidly if the liver is intact (Meek) . 



Since fibrinogen is readily soluble in dilute saline solutions, and 

 fibrin only soluble with great difficulty, we may say that in coagu- 

 lation of the blood a substance soluble in the plasma passes into an 

 insoluble form. How is this change determined when blood is 

 shed ? We have said that a solution of pure fibrinogen can be 

 made to coagulate, but it does not coagulate of itself. The addition 

 of another substance in minute quantity is necessary. This sub- 

 stance, to which the name thrombin has been applied, can be 

 obtained in various ways, although not in a state of purity; for 

 example, by precipitating blood-serum, or defibrinated blood, with 

 fifteen to twenty times its bulk of alcohol, letting the whole stand 

 for a month or more, and then extracting the precipitate with 

 water. All the ordinary proteins of the blood having been ren- 

 dered insoluble by the alcohol, the thrombin passes into solution 

 in the water, and the addition of a trace of the extract to a solution 

 of fibrinogen causes coagulation. When purified as well as possible, 

 thrombin still gives protein reactions, but it is not known whether 

 it is really a protein. 



The action of thrombin on fibrinogen helps to explain many 

 experiments in coagulation. Thus, transudations like hydrocele 

 fluid do not clot spontaneously, although they contain fibrinogen, 



