HEMOPHILIA 247 



apparently this is due to a reaction on the part of the organism 

 to the loss of blood. If blood is collected directly from the 

 site of bleeding the coagulation time is very rapid, because of 

 the accumulation of fibrin ferment from the clot over which the 

 escaping blood flows. Yet in spite of the normal coagulability 

 of the blood and the rapid clotting after the blood escapes from 

 the vessel, bleeding continues for long periods before it can be 

 stopped. As there is no general change in the properties of the 

 blood to account for the bleeding, and as local influences seem 

 to be important in hemophilia, Sahli advances the plausible 

 hypothesis that chemical changes in the vessels must be the 

 essential factor in hemophilia. Hemorrhage is ordinarily 

 checked chiefly by the formation of clots that plug up the bleed- 

 ing vessels at the point of the hemorrhage. The local formation 

 of a clot is believed to be due to liberation of fibrin-ferment (or 

 its antecedents) by the injured cells of the vessel- wall at the 

 point of the vascular lesion. If the cells of the vessel- wall are 

 deficient in these fibrin-forming substances, the blood will not 

 clot in the mouths of the vessels, but will first clot when it 

 reaches a place where fibrin-forming substances are furnished by 

 other tissues, or, as is generally the case, when the leucocytes 

 are broken up by exposure to the air or other injurious influ- 

 ences so that they liberate fibrin-ferment. Under these condi- 

 tions the blood may clot in large masses, but as there is no 

 fibrin adhering to the vessel-walls at the bleeding openings, 

 blood continues to escape. Sahli considers, therefore, that the 

 cause of hemophilia lies in hereditary deficiency of the fibrin- 

 forming substances, thrombokinase or zymoplastic substance 

 ( see " Thrombosis "), in the vessel- walls, so that when the vessels 

 are injured there is no local production of fibrin such as occurs 

 normally. Local hemophilia may be explained readily as a 

 local deficiency in fibrinoplastic material. In general hemo- 

 philia even the leucocytes may exhibit the same defect, in which 

 case clotting of the blood is diminished even outside the tissues. 

 This hypothesis seems to be in excellent agreement with the 

 facts now known, but there yet remains to be demonstrated 

 such a lack of fibrin-forming elements in the vessel-walls and 

 other tissues of a hemophilic subject. This hypothesis perhaps 

 also explains why the marked increase in coagulability of 

 the blood obtained by administration of calcium salts (Wright l ) 

 is, as "Wright's observations show, not sufficient alone to stop 

 hemophilic bleeding, even though the rapidity of clotting is 

 much greater than normal. 



1 Brit. Med. Jour., 1894 (ii), 57. 



