300 DISTURBANCES OF CIRCULATION 



ing, 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, thi'om- 

 bokinase 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 

 hemophilia 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 many of the facts 

 now known, but there yet remains to be demonstrated such a lack ol" 

 fibrin-forming elements in the vessel-walls and other tissues of a hemo- 

 philic subject, and a single autopsy of a hemolytic subject gave, on the 

 contrary, a very active thromboplastic extract from the vessels 

 (Gressot).^^ The tissues of one case studied by Lowenburg and 

 Rubenstone,*^ however, showed in the liver and thyroid a decreased 

 capacity to accelerate coagulation. 



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 hemopliilia 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 hemopliilia. Fonio, and jXIinot and Lee, 

 however, find that the blood platelets of hemophihcs 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 

 activity on the part of the platelets in spite of their occurrence in nor- 

 mal numbers in hemopliilia. The significance of the platelets is shown 

 especially clearly by the observation of Ledingham and Bedson*^ 

 that antiplatelet serum will produce a purpuric condition when in- 

 jected into animals of the species furnishing the platelets, although 

 no similar effect is produced by antileucocj'te or antierythrocyto 

 serum, Hess^^ states that there may be an hereditary purjnira, 

 sometimes occurring in the females of hemophilic families, difl'ering 

 from hemophilia in a deficiency in the number of platelets, hemor- 

 rhages following local congestions or puncture wounds and exhibiting 

 an increase in the "bleeding time." 



"Zeit. klin. Med., 1912 (76), 194. Since corroborated bv Minot and Lee." 



"Jour. A.mer. Med. Assoc, 1918 (71), 1196. 



*' HowoU, .Vroh. Int. Med.; 1914 (VA), Tti; llurwitz and Lucas, ibid., 1916 (17), 

 543; Minot and Lee, ibi<l., lUKi (18), 474; Klingcr, Zeit. klin. Med., 1918 (86) 

 335; Pcttibonc, Jour. Lab. Clin. Sled., 1918 (3), 275; these papers review recent 

 work on hemophilia. 



■•* Lancet, Feb. 13, 1915. Similar observations have been made by Watabiki 

 (Kitasato's Arch. Exp. Med., 1917 (1), 195). 



"Arch. Int. Med., 1916 (17), 203. 



