iiKMoi'iiii.ix 299 



■'blectliii^' time"" t'ullowing puiiclurcs in tliu skin is not excessive. As 

 to the rate of clotting, Sahli,-° who avoided a number of errors made 

 in earlier investio-ations, found that in the intervals between the at- 

 tacks of hemorrhafi-c the rate of the coa^'ulation of the blood is con- 

 stantly Huicli slower than noi-iiial. Dui'iii;^- an attack of bleeding the 

 coagulation time approaches the normal ; indeed, it may be faster 

 than normal ; 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 ac- 

 cumulation of fibrin ferment from the clot over which the escaping 

 blood flows. Yet in spite of the normal coagidability 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 he found 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 advanced the plausible hypothesis that the cause of hemophilia 

 lies in hereditary deficiency of the fibrin-forming substances, throm- 

 bokinase or zymoplastic substance (see "Thrombosis"), in the vessel- 

 walls, so that when the vessels are injured there is no local produc- 

 tion of fibrin such as occurs normally. Local hemo])hilia may be ex- 

 plained readily as a local deficiency in fibrinoplastic material. In 

 general hemophilia even the leucocytes may exhibit the same defect, 

 in which case clotting of the blood is diminished even outside the tis- 

 sues. This hypothesis seems to be in excellent agreement with many 

 of 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, and a single autopsy of a hemolytic 

 subject gave, on the contrarj^ a very active thromboplastic extract from 

 the vessels fGressot).-^ 



"With the improved methods of study of the factors in coagulation 

 of blood introduced by Howell, it has been found by him and cor- 

 roborated by others ^° that in hemophilia there is constantly a defi- 

 ciency in prothrombin, the other factors being practically normal in 

 amount, and as in other hemorrhagic conditions there is no equal 

 alteration in the prothrombin, they look upon this change as an 

 essential characteristic of hemophilia. Fonio, and ]\Iinot and Lee, 

 however, find that the blond platelets of hemophilics are remarkably 

 ineffective in causing coagulation of either normal or hemophilic 

 plasma, although normal platelets cause normal coagulation of hemo- 

 philic plasma, and therefore conclude that there is some deficient ac- 

 tivity on the part of the platelets in spite of their occurrence in normal 

 luimbers in hemophilia. The significance of the platelets is shown 



20 Zeit. klin. Med., 1012 (70), 104. Since corroborated by Minot and Lee. 



30 Howell, Arch. Int. Med., 1014 (1.3), 76; Hurwitz and Lucas. ihicL. 1016 (17), 

 543: ^linot and Lee, ihid., 1010 (18), 474; these papers review re<'ent work on 

 hemophilia. 



