682 CHARLES W. HOOPER 



9 



antithrombin are normal constituents of the circulating blood and to- 

 gether fulfill the function of safeguarding the fluidity of the blood ; that is 

 to say, of preventing intravascular clotting. The pro-ant ithrombin by its 

 conversion to antithrombin provides a protection against any small quan- 

 tities of thrombin that may arise in the circulating blood. The heparin 

 in addition to functioning as a specific activator to pro-antithrombin exerts 

 an inhibiting influence upon the conversion of prothrombin to active throm- 

 bin. When blood is shed or when in other ways thromboplastic substances 

 (cephalin) are added to the blood, the protection afforded by the heparin 

 is overcome and thrombin is formed in amounts sufficient to cause clotting. 

 It is also suggested that variations in the amount of heparin in the blood 

 may suffice to explain some of the known abnormalities in coagulation, 

 hemophilia, for example. Blood to which heparin has been added in 

 amount sufficient to cause a marked slowing of the time of coagulation, 

 presents a picture which is identical with that exhibited by hemophilic 

 bloods. There is the same prolongation of the time of spontaneous coagu- 

 lation, the same retardation in the prothrombin time and the same ten- 

 dency toward an increase in antithrombic action. 



Addis (1911) presented experimental proof that the hemophilic con- 

 dition is due to a retardation in the activation of prothrombin to thrombin, 

 corresponding in degree to the delay in the coagulation of the blood. How- 

 ever, he failed to find a substance in hemophilic blood, not present in 

 normal blood, which hirfdered the activation of prothrombin and attribut- 

 ed the condition to a qualitative defect in the prothrombin itself. Howell 

 (1914) and Hurwitz and Lucas (1916) have also shown that the char- 

 acteristic peculiarity of hemophilic blood is its markedly delayed time of 

 coagulation, which they attribute to a diminution in amount of the pro- 

 thrombin resulting in a relative excess of antithrombin. Howell and 

 Holt's suggestion in 1918 that the condition of hemophilia may be duo to 

 an abnormal amount of heparin in the blood, should be submitted to experi- 

 mental examination as soon as an adequate method is devised for the esti- 

 mation of heparin in circulating blood. 



Fibrinojjen as a Hepatic Internal Secretion 



Eibrinogen is a globulin-like body present in the normal blood in 

 fairly constant amounts; it may be considered as an internal secretion 

 elaborated by the liver. It gives rise to an insoluble protein, fibrin, the 

 formation of which is the essential phenomenon in the coagulation of 

 blood, in that it forms the body and main bulk of the clot. If this sub- 

 stance is reduced in the blood there is no abnormality in the process of 

 blood-clotting, but the formed clot is more or less flabby, depending on the 

 amount of reduction. Jacoby (1900), Doyon, Morel and Kereff (1905) 



