{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T23:18:32Z","timestamp":1670627912124},"reference-count":198,"publisher":"University of Toronto Press Inc. (UTPress)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Canadian Bulletin of Medical History"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:p> Treatment of the bleeding disorder hemophilia in the nineteenth century was empirical, based on clinical experience. Medications, transfusions of human or animal blood, and injections of blood sera were utilized in an attempt to halt life-threatening hemorrhages. After 1900, the application of clinical laboratory science facilitated the utilization of anti-coagulated blood and donor blood compatibility tests for safer emergency transfusions. But repeated transfusions produced blood incompatibility that limited future utilization. Investigation of hormones and snake venom as coagulants appeared hopeful during the 1930s, but plasma globulin research during World War II resulted in the isolation of antihemophilic factors that promptly reduced hemorrhage. Their application to bleeding episodes resulted in a more normal life for hemophiliacs after 1950. <\/jats:p>","DOI":"10.3138\/cbmh.386-092019","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T23:28:16Z","timestamp":1585092496000},"page":"119-146","source":"Crossref","is-referenced-by-count":1,"title":["\u201cWhatever Works\u201d: Innovations in the Treatment of Hemophilia in the United States 1783\u20131950"],"prefix":"10.3138","volume":"37","author":[{"given":"Alan R.","family":"Rushton","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hunterdon Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1696","reference":[{"key":"fn1","unstructured":"A.A. 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Rafnoff and Bruce Bennett, \"The Genetics of Hereditary Disorders of Blood Coagulation,\" Science 179 (1973): 1291-98","DOI":"10.1126\/science.179.4080.1291"},{"key":"#cr-split#-fn19.2","doi-asserted-by":"crossref","unstructured":"Pier M. Mannucci and Edward G. D. Tuddenham, \"The Hemophilias: From Royal Genes to Gene Therapy,\" New England Journal of Medicine 344 (2001): 1773-79.","DOI":"10.1056\/NEJM200106073442307"},{"key":"fn20","doi-asserted-by":"crossref","unstructured":"Augusto B. Federici, Christine A. Lee, Erik Berntorp, David Lillicrap, and Robert R. Montgomery, Von Willebrand Disease: Basic and Clinical Aspects (Chichester: Wiley\u2013Blackwell, 2011).","DOI":"10.1002\/9781444329926"},{"key":"#cr-split#-fn21.1","unstructured":"Reynell Coates, \"Observations on Hereditary Hemorrhage,\" North American Medical and Surgical Journal 6 (1828): 37"},{"key":"#cr-split#-fn21.2","unstructured":"Gideon Humphrey, \"An Account of an Extraordinary Predisposition to Haemorrhage in a Family of Children,\" The Medical Review and Analectic Journal 1\u00a0(1824): 278."},{"key":"#cr-split#-fn22.1","unstructured":"James N. Hughes, \"A Case of Hereditary Hemorrhagic Tendency,\" Transylvania Journal of Medicine and the Associate Sciences 5 (1832): 133"},{"key":"#cr-split#-fn22.2","doi-asserted-by":"crossref","unstructured":"\"A Case of Hereditary Hemorrhagic Tendency,\" Boston Medical and Surgical Journal 7 (1832): 220-21.","DOI":"10.1056\/NEJM183205160061402"},{"key":"fn23","doi-asserted-by":"crossref","unstructured":"C.B. Kerr, \u201cThe Fortune of Haemophiliacs in the Nineteenth Century,\u201d Medical History 7 (1963): 359\u201370, 359.","DOI":"10.1017\/S0025727300028829"},{"key":"fn24","unstructured":"Kerr, \u201cThe Fortune of Haemophiliacs,\u201d 361."},{"key":"fn25","unstructured":"James Blundell, \u201cTransfusion of Blood,\u201d Philadelphia Journal of Medicine and Physical Science 11 (1825): 205\u20137, 207; George Edwards, \u201cPhilip Syng Physick,\u201d Proceedings of the Royal Society of Medicine 33 (1940): 145\u201348; James Polk Morris, \u201cBlood, Bleeding and Blood Transfusion in Mid-Nineteenth Century America,\u201d PhD diss., University of Michigan, 1974."},{"key":"fn26","doi-asserted-by":"crossref","unstructured":"Blundell; W. 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Rothstein, American Physicians in the 19th Century (Baltimore, MD: Johns Hopkins University, 1972), 122-26"},{"key":"#cr-split#-fn30.2","unstructured":"Eliot Freidson, Profession of Medicine: A Study of the Sociology of Applied Knowledge (Chicago: University of Chicago Press, 1988), 168-70"},{"key":"#cr-split#-fn30.3","unstructured":"John H. Warner, \"The Fall and Rise of Professional Mystery: Epistemology, Authority and the Emergence of Laboratory Medicine in Nineteenth-Century America,\" in Andrew Cunningham and Percy Williams, eds. The Laboratory Evolution in Medicine (Cambridge: Cambridge University Press, 1992), 110-41, 130."},{"key":"fn31","doi-asserted-by":"crossref","unstructured":"Thomas D. Dunn, \u201cHemophilia,\u201d American Journal of the Medical Sciences 85 (1883): 68\u201383, 80.","DOI":"10.1097\/00000441-188301000-00004"},{"key":"fn32","unstructured":"R.F. Harris, \u201cHemophilia,\u201d Philadelphia Medical Times 2 (1872): 273\u201375."},{"key":"fn33","unstructured":"\u201cSingular Story of a Massachusetts Family,\u201d The True Northerner, 27 August 1875."},{"key":"#cr-split#-fn34.1","unstructured":"Leonard Landois, Die Transfusion des Blutes (Leipzig: FCW Vogel, 1875), 118"},{"key":"#cr-split#-fn34.2","doi-asserted-by":"crossref","unstructured":"Paul L. F. Giangrande, \"The History of Blood Transfusion,\" British Journal of Hematology 110 (2000): 758-67.","DOI":"10.1046\/j.1365-2141.2000.02139.x"},{"key":"fn35","unstructured":"Pemberton, The Bleeding Disease, 54."},{"key":"fn36","unstructured":"Thomas G. Morton, \u201cOn Transfusion of Blood,\u201d American Journal of the Medical Sciences 68 (1874): 110\u201313. Whipping of the donor blood removed most of its clotting factors. The transfusion replaced blood volume but may not actually have done much to improve coagulation."},{"key":"fn37","unstructured":"Joseph Roussel, Transfusion of Human Blood (London: J and A Churchill, 1877), 70\u201371."},{"key":"fn38","unstructured":"\u201cApparatus for the Performance of Direct Transfusion,\u201d Monthly Abstract of Medical Science 4 (1877): 88\u201390."},{"key":"fn39","doi-asserted-by":"crossref","unstructured":"Francoise Angeline Roux, P. 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Diamond, \u201cA\u00a0History of Blood Transfusion,\u201d in Maxwell M. Wintrobe, ed. Blood, Pure and Eloquent (New York: McGraw\u2013Hill, 1980), 659\u201390, 664."},{"key":"fn43","unstructured":"Jean-Baptiste Denis, \u201cAn Extract from a Letter,\u201d Philosophical Transactions 1 (1666): 617\u201323; \u201cAn Extract of a Printed Letter,\u201d Philosophical Transactions 3 (1667): 710\u201315; Starr, Blood, 3\u20136; Moore, Blood and Justice, 3\u20136, 150\u201359; P. Learoyd, \u201cThe History of Blood Transfusion Prior to the 20th Century, I,\u201d Transfusion Medicine 22 (2012): 308\u201314."},{"key":"fn44","unstructured":"Denis, \u201cAn Extract of a Printed Letter,\u201d 715."},{"key":"fn45","unstructured":"Pierre Cyprien Ore, Etudes historiques et physiologiques sur la transfusion du sang (Paris: J.B. 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Dedolph, \u201cTransfusion in a Case of Haemophilia,\u201d Transaction of the Minnesota Medical Society 14 (1882): 89\u201390; \u201cTransfusion of Blood,\u201d St. Paul Daily Globe 19 June 1879; \u201cEine interessante Operation,\u201d Der Nordstern, 29 May 1879."},{"key":"#cr-split#-fn49.1","unstructured":"\"Chloride of Lime in Hemophilia,\" Cincinnati Lancet Clinic 41 (1898): 581"},{"key":"#cr-split#-fn49.2","unstructured":"Henry M. Bannister, \"Haemophilia,\" in Hugo von Ziemssen, ed. Cyclopedia of Practical Medicine, vol. Supplement (New York: W. Wood, 1881), 785"},{"key":"#cr-split#-fn49.3","unstructured":"William Osler, \"Hemophilia,\" in William Pepper, ed. System of Medicine, vol. 3 (Philadelphia: Lea Brothers, 1885), 931-39."},{"key":"#cr-split#-fn50.1","doi-asserted-by":"crossref","unstructured":"Rudolf Virchow, \"\u00dcber die Standpunkte in der wissenschaftlichen Medicin,\" Archiv f\u00fcr pathologische Anatomie und Physiologie und f\u00fcr klinische Medicin 1 (1847): 3-19, 16-17","DOI":"10.1007\/BF01975521"},{"key":"#cr-split#-fn50.2","unstructured":"A. McGehee Harvey, Science at the Bedside. Clinical Research in American Medicine 1905-1945 (Baltimore, MD: Johns Hopkins University, 1981), 18-30."},{"key":"#cr-split#-fn51.1","unstructured":"Stanley Reiser, Medicine and the Reign of Technology (Cambridge: Cambridge University Press, 1978), 127-40"},{"key":"#cr-split#-fn51.2","unstructured":"Lester S. King, Transformations in American Medicine (Baltimore, MD: Johns Hopkins University Press, 1991), 224-25."},{"key":"fn52","doi-asserted-by":"crossref","unstructured":"Samuel E.D. Shortt, \u201cPhysicians, Science and Status: Issues in the Professionalization of Anglo-American Medicine in the Nineteenth Century,\u201d Medical History 27 (1983): 51\u201368, 65.","DOI":"10.1017\/S0025727300042265"},{"key":"fn53","unstructured":"Warner, \u201cThe Fall and Rise of Professional Mystery,\u201d 110\u201312."},{"key":"#cr-split#-fn54.1","doi-asserted-by":"crossref","unstructured":"John H. Warner, \"Ideals of Science and Their Discontentments in Late Nineteenth-Century American Medicine,\" Isis 82 (1991): 454-78","DOI":"10.1086\/355837"},{"key":"#cr-split#-fn54.2","doi-asserted-by":"crossref","unstructured":"Michael Worboys, \"Practice and the Science of Medicine in the Nineteenth Century,\" Isis 102 (2011): 109-15.","DOI":"10.1086\/658660"},{"key":"fn55","unstructured":"\u201cBleeding to Death,\u201d The Morning Call, 6 October 1890."},{"key":"fn56","unstructured":"\u201cThe Effect of Calcium Chloride on the Blood,\u201d University Medical Magazine 6 (1893): 132."},{"key":"#cr-split#-fn57.1","unstructured":"Judson Daland and W. Duffield Robinson, \"A Clinical Study of 3 Cases of Spontaneous Hemophilia in Brothers,\" American Therapist 3 (1895): 215-29"},{"key":"#cr-split#-fn57.2","unstructured":"Judson Daland, \"Three Cases of Spontaneous Hemophilia,\" Boston Medical and Surgical Journal 132 (1898): 263-64."},{"key":"fn58","unstructured":"\u201cInfluence of Carbon Dioxide and Oxygen on Blood Coagulation,\u201d Buffalo Medical and Surgical Journal 35 (1895): 158."},{"key":"#cr-split#-fn59.1","unstructured":"\"Treatment of Hemophilia,\" Atlanta Medical and Surgical Journal 13 (1896): 483-85"},{"key":"#cr-split#-fn59.2","doi-asserted-by":"crossref","unstructured":"H.F. Vickery, \"Hemophilia,\" Boston Medical and Surgical Journal 136 (1897): 226-28.","DOI":"10.1056\/NEJM189703111361002"},{"key":"fn60","unstructured":"A. Pigot, \u201cSur un cas de purpura hemorrhagique gueri par des injections de serum artificiel,\u201d Gazette Hebdomadaire de Medecine et de Chururgie Ser 3 Vol 2 (1897): 990."},{"key":"fn61","unstructured":"Albert Fry, \u201cSuccessful Treatment of Hemophilia with Injection of Serum,\u201d Medical Record 54 (1898): 131."},{"key":"#cr-split#-fn62.1","unstructured":"P. Emile Weil, \"L'hemophilie, pathogenie et serotherapie,\" Presse medicale 13 (1905): 581"},{"key":"#cr-split#-fn62.2","unstructured":"P. Broca, \"Die Blutstillung bei der H\u00e4mophilen durch Injektionen mit frischem tierischen Serum,\" Medizinishe Klinic: Wochenschrift f\u00fcr praktische \u00c4rzte 3 (1907): 1445-48."},{"key":"fn63","unstructured":"Vaccine and Serum Therapy (New York: Lederle Antitoxin Laboratory, 1914); A.W. Lescohier, \u201cSerum Treatment of Hemorrhage and Blood Dyscrasias,\u201d New York Medical Journal 95 (1912): 223\u201329."},{"key":"#cr-split#-fn64.1","doi-asserted-by":"crossref","unstructured":"Timothy Leary, \"The Use of Fresh Animal Sera in Hemorrhagic Conditions,\" Boston Medical and Surgical Journal 159 (1908): 73-79","DOI":"10.1056\/NEJM190807161590302"},{"key":"#cr-split#-fn64.2","unstructured":"E.B. Probasco, \"Review of the Recent Work on the Use of Normal Serum in Hemorrhage,\" New York State Medical Journal 12 (1911): 32-34."},{"key":"fn65","doi-asserted-by":"crossref","unstructured":"M.J. Perkins, \u201cDiphtheric Serum Used to Control Bleeding in a Hemophiliac,\u201d Journal of the American Medical Association 59 (1912): 1539\u201340.","DOI":"10.1001\/jama.1912.04270100307018"},{"key":"fn66","unstructured":"Charles R. Grandy, \u201cSerum Treatment of Hemorrhagic Disease,\u201d Charlotte Medical Journal 68 (1913): 13\u201315."},{"key":"fn67","unstructured":"G.F. Dolmage, \u201cA Case of Hemophilia Treated with Horse Serum,\u201d Journal of the Iowa State Medical Society 5 (1915): 107."},{"key":"fn68","doi-asserted-by":"crossref","unstructured":"A.H. Traver, \u201cHemophilia Treated by Human Blood Serum,\u201d Journal of the American Medical Association 60 (1913): 44.","DOI":"10.1001\/jama.1913.04340010046017"},{"key":"fn69","doi-asserted-by":"crossref","unstructured":"Leonard K. Hirschberg, \u201cThe New Serum Treatment of Bleeding and Hemorrhage,\u201d Scientific American 107 (1912): 168.","DOI":"10.1038\/scientificamerican08241912-168"},{"key":"#cr-split#-fn70.1","unstructured":"\"Arrest of Hemorrhage in Hemophilia,\" Medical and Surgical Reporter 77 (1897): 672"},{"key":"#cr-split#-fn70.2","unstructured":"\"A New Method of Treating Hemophilia,\" Western Medical Reformer 59 (1899): 155."},{"key":"fn71","doi-asserted-by":"crossref","unstructured":"J.H. Sayer, \u201cHemophilic Bleeding Checked by Foreign Blood,\u201d Journal of the American Medical Association 58 (1912): 106.","DOI":"10.1001\/jama.1912.04260010108015"},{"key":"fn72","doi-asserted-by":"crossref","unstructured":"O. Heyfelder, \u201cZur Lehre von der Transfusion,\u201d Deutsche Zeitschrift f\u00fcr Chirurgie 5 (1875): 108\u201319.","DOI":"10.1007\/BF02794252"},{"key":"fn73","doi-asserted-by":"crossref","unstructured":"Alexis Carrel and Charles C. Guthrie, \u201cAnastomosis of Blood Vessels by the Patching Technique and Transplantation of the Kidney,\u201d Journal of the American Medical Association 47 (1906): 1648\u201351.","DOI":"10.1001\/jama.1906.25210200044001h"},{"key":"fn74","doi-asserted-by":"crossref","unstructured":"George Crile, \u201cThe Technique of Direct Transfusion of Blood,\u201d Annals of Surgery 46 (1907): 329\u201332.","DOI":"10.1097\/00000658-190709000-00001"},{"key":"fn75","unstructured":"Pemberton, The Bleeding Disease, 64."},{"key":"fn76","unstructured":"George Crile, \u201cPreliminary Note on the Direct Transfusion of Blood,\u201d Cleveland Medical Journal 6 (1907): 112\u201315; \u201cOn the Direct Transfusion of Blood,\u201d Canada Lancet 40 (1906\u20137): 1057\u201368."},{"key":"fn77","unstructured":"George Crile, Hemorrhage and Transfusion (New York: D. Appleton, 1909), 534."},{"key":"#cr-split#-fn78.1","doi-asserted-by":"crossref","unstructured":"Francis Allen, \"Hemophilia Treated by Transfusion,\" Annals of Surgery 48 (1908): 625-26","DOI":"10.1097\/00000658-190810000-00013"},{"key":"#cr-split#-fn78.2","unstructured":"A.A. Berg, \"Direct Blood Transfusion,\" Medical Record 75 (1909): 514-17"},{"key":"#cr-split#-fn78.3","unstructured":"Milton Hahn, \"Hemophilia Treated by Transfusion,\" Medical Record 78 (1910): 624-25."},{"key":"fn79","doi-asserted-by":"crossref","unstructured":"Charles Goodman, \u201cBlood Transfusion in Hemophilia,\u201d Annals of Surgery 52 (1910): 457\u201362; \u201cSuccessful Case of Transfusion at Beth Israel Hospital,\u201d The Sun, 14 July 1909.","DOI":"10.1097\/00000658-191010000-00002"},{"key":"fn80","doi-asserted-by":"crossref","unstructured":"William Pepper and Verner Nisbet, \u201cA Case of Fatal Hemolysis Following Direct Transfusion of Blood by Arteriovenous Anastamosis,\u201d Journal of the American Medical Association 49 (1907): 385\u201389.","DOI":"10.1001\/jama.1907.25320050023002d"},{"key":"#cr-split#-fn81.1","unstructured":"Karl Landsteiner, \"\u00dcber Agglutinationerscheinungen normalen menschlichen Blutes,\" Wiener klinische Wochenschrift 14 (1901): 1132-34"},{"key":"#cr-split#-fn81.2","unstructured":"Alfred von Decastello and Adriano Sturli, \"\u00dcber die Isoagglutinine im Serum gesunder und kranker Menschen,\" M\u00fcnchener medizinische Wochenschrift 49 (1902): 1090-95."},{"key":"#cr-split#-fn82.1","unstructured":"Martin Rehling and Richard Weil, \"The Avoidance of Hemolysis in Transfusion,\" American Journal of Surgery 23 (1909): 96-98"},{"key":"#cr-split#-fn82.2","unstructured":"John Funke, \"Test to Determine the Adaptability of the Donor's Blood to the Receiver's Blood in Transfusion,\" The Therapeutic Gazette 24 (1908): 457-60."},{"key":"fn83","doi-asserted-by":"crossref","unstructured":"George R. Minot, \u201cMethods for Testing Donors for Transfusion of Blood,\u201d Boston Medical and Surgical Journal 174 (1916): 667\u201374.","DOI":"10.1056\/NEJM191605111741901"},{"key":"fn84","unstructured":"W.L. Moss and J. Gelien, \u201cSerum Treatment of Hemorrhagic Diseases,\u201d Johns Hopkins Hospital Bulletin 22 (1911): 272\u201378."},{"key":"#cr-split#-fn85.1","unstructured":"George M. Dorrance and Nate Ginsburg, \"Transfusion: History, Development, Present Status and Techniques of Operation,\" New York Medical Journal 87 (1908): 941-44"},{"key":"#cr-split#-fn85.2","doi-asserted-by":"crossref","unstructured":"Thomas B. Cooley, \"The Treatment of Hemorrhagic Disorders,\" Journal of the American Medical Association 61 (1913): 1277-81.","DOI":"10.1001\/jama.1913.04350150033011"},{"key":"fn86","doi-asserted-by":"crossref","unstructured":"W.L. 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