Editing Haemophilia (section)

==History==
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|quote=About seventy or eighty years ago, a woman by name of Smith, settled in the vicinity of Plymouth, New Hampshire, and transmitted the following idiosyncrasy to her descendants. It is one, she observed, to which her family is unfortunately subject, and had been the source not only of great solicitude, but frequently the cause of death. If the least scratch is made on the skin of some of them, as mortal a hemorrhagy will eventually ensue as if the largest wound is inflicted. (...) So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation.|source=John C. Otto, 1803<ref>{{cite web |url=http://www.genmedhist.info/articles-and-papers/ |title=Otto JC. The Medical Repository. 1803; Vol VI (1): 1–4 |publisher=Genmedhist.info |access-date=2013-11-21 |url-status=live |archive-url=https://web.archive.org/web/20140904144726/http://www.genmedhist.info/articles-and-papers/ |archive-date=2014-09-04 }}</ref>
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===Scientific discovery===
The excessive bleeding was known to ancient people. The [[Talmud]] instructs that a boy must not be circumcised if he had two brothers who died due to complications arising from their circumcisions, and [[Maimonides]] says that this excluded paternal half-brothers.<ref>Mishne Torah, laws of circumcision, chapter 1 law 18. It explicitly talks about multiple boys who have the same mother, regardless of whether or not they also have the same father.</ref> This may have been due to a concern about haemophilia.<ref>Singer, Isidore; et al., eds. (1901–1906). "Morbidity". The Jewish Encyclopedia. New York: Funk & Wagnalls.</ref> The tenth century Arab surgeon [[Al-Zahrawi]] noted cases of excessive bleeding among men in a village. Several similar references to the disease later known as haemophilia appear throughout historical writings, though no term for inherited abnormal bleeding tendencies existed until the nineteenth century.<ref>{{cite book|chapter=Clinical Manifestations and Therapy of Inherited and Acquired Hemophilia|last1=Tuddenham|first1=EG|last2=Collins|first2=P|last3=Yee|first3=TT|year=2012|title=Hemostasis and Thrombosis: Basic Principles and Clinical Practice|isbn=978-1-4511-7769-5|publisher=Wolters Kluwer Health|editor-last1=Marder|editor-first1=VJ|editor-first2=WC|editor-last2=Aird|editor-first3=S|editor-last3=Bennett|editor-first4=Sam|editor-last4=Schulman|editor-first5=Gilbert|editor-last5=White}}</ref>

In 1803, [[John Conrad Otto]], a Philadelphian physician, wrote an account about "a hemorrhagic disposition existing in certain families" in which he called the affected males "bleeders".<ref name=nilsson>{{cite journal | author = Nilsson IM | title = Haemophilia—then and now | journal = Sydsvenska Medicinhistoriska Sallskapets Arsskrift | volume = 31 | pages = 33–52 | year = 1994 | pmid = 11640407 }}</ref> He recognised that the disorder was hereditary and that it affected mostly males and was passed down by healthy females. His paper was the second paper to describe important characteristics of an X-linked genetic disorder (the first paper being a description of [[color blindness|colour blindness]] by [[John Dalton]] who studied his own family). Otto was able to trace the disease back to a woman who settled near Plymouth, New Hampshire, in 1720. The idea that affected males could pass the trait onto their unaffected daughters was not described until 1813 when John F. Hay published an account in ''[[The New England Journal of Medicine]]''.<ref>[http://www.genmedhist.info/Articles%20and%20Papers/ DIGITISED EARLY PAPERS AND BOOKS ON HUMAN AND MEDICAL GENETICS] {{webarchive|url=https://web.archive.org/web/20110721202446/http://www.genmedhist.info/Articles%20and%20Papers/ |date=21 July 2011 }} Genetics and Medicine Historical Network, Cardiff University.</ref><ref>{{cite journal|author=Hay J|title=Account of a remarkable hæmorrhagic disposition, existing in many individuals of the same family |journal=N Engl J Med Surg|volume=2|issue=3 |pages=221–5|date=July 1813|doi=10.1056/NEJM181307010020302|pmid=30493599 |pmc=5581570 |url=https://zenodo.org/record/1620327 }}</ref>

In 1924, a Finnish doctor discovered a hereditary bleeding disorder similar to haemophilia localised in [[Åland]], southwest of Finland.<ref>{{cite journal|title=Haemophilia Special Issue: von Willebrand's Disease: a Report from a Meeting in the Åland Islands|doi=10.1111/hae.2012.18.issue-s6|volume=18|journal=Haemophilia|year = 2012|issue=s6 }}</ref> This bleeding disorder is called [[Von Willebrand factor#History|"Von Willebrand Disease"]].

The term "haemophilia" is derived from the term "haemorrhaphilia" which was used in a description of the condition written by [[Friedrich Hopff]] in 1828, while he was a student at the [[University of Zurich]].<ref name=nilsson/><ref name="History">{{cite web|url=http://www.wfh.org/2/1/1_1_3_HistoryHemophilia.htm|title=The History of hemophilia|access-date=5 June 2009|url-status=dead|archive-url=https://web.archive.org/web/20090331042700/http://www.wfh.org/2/1/1_1_3_HistoryHemophilia.htm|archive-date=31 March 2009}}</ref> In 1937, Patek and Taylor, two doctors from [[Harvard University]], discovered anti-haemophilic globulin.<ref name=blood>[https://books.google.com/books?id=H85dwxYTKLwC&q=Judah+the+Patriarch+hemophilia+Talmud&pg=RA1-PA1195 Chapter 38 Coagulation Factors V and VIII by GC White and GE Gilbert] {{webarchive|url=https://web.archive.org/web/20170911010926/https://books.google.com/books?id=H85dwxYTKLwC&pg=RA1-PA1195 |date=11 September 2017 }} in ''Blood: principles and practice of hematology: 2nd edition''. 2003. Eds. Robert I. Handin, Samuel E. Lux, Thomas P. Stossel. {{ISBN|978-0-7817-1993-3}}.</ref> In 1947, [[Alfredo Pavlovsky]], a doctor from Buenos Aires, found haemophilia A and haemophilia B to be separate diseases by doing a lab test. This test was done by transferring the blood of one haemophiliac to another haemophiliac. The fact that this corrected the clotting problem showed that there was more than one form of haemophilia.<ref>{{Cite journal |last=Schramm |first=Wolfgang |date=2014 |title=The history of haemophilia – a short review |url=https://pubmed.ncbi.nlm.nih.gov/24513149/#:~:text=The%20history%20of%20haemophilia%20dates,the%20only%20possible%20treatment%20option. |journal=Thrombosis Research |volume=134 |issue=Suppl 1 |pages=S4–9 |doi=10.1016/j.thromres.2013.10.020 |issn=1879-2472 |pmid=24513149}}</ref>

===European royalty===
{{main|Haemophilia in European royalty}}
[[File:Erbgang Bluterkrankheit.svg|thumb|upright=1.8|Haemophilia in European royalty]]
Haemophilia has featured prominently [[Haemophilia in European royalty|in European royalty]] and thus is sometimes known as 'the royal disease'. [[Queen Victoria]] passed the mutation for haemophilia B<ref>{{cite news|author=Michael Price|title=Case Closed: Famous Royals Suffered From Hemophilia|url=http://sciencenow.sciencemag.org/cgi/content/full/2009/1008/2|newspaper=ScienceNOW Daily News|publisher=AAAS|date=8 October 2009|access-date=9 October 2009|url-status=dead|archive-url=https://web.archive.org/web/20091012020300/http://sciencenow.sciencemag.org/cgi/content/full/2009/1008/2|archive-date=12 October 2009}}</ref><ref>{{cite journal|author=Evgeny I. Rogaev|title=Genotype Analysis Identifies the Cause of the 'Royal Disease'|journal=Science|volume=326|issue=5954|pages=817|date=8 October 2009|display-authors=etal|doi=10.1126/science.1180660|pmid=19815722|bibcode=2009Sci...326..817R|s2cid=206522975|doi-access=free}}</ref> to her son [[Leopold, Duke of Albany|Leopold]] and, through two of her daughters, Alice and Beatrice, to various royals across the continent, including the royal families of [[House of Bourbon|Spain]], [[Hohenzollern|Germany]], and [[Romanov|Russia]]. In Russia, [[Alexei Nikolaevich, Tsarevich of Russia|Tsarevich Alexei]], the son and heir of [[Nicholas II of Russia|Tsar Nicholas II]], famously had haemophilia, which he had inherited from his mother, [[Alexandra Feodorovna (Alix of Hesse)|Empress Alexandra]], one of Queen Victoria's granddaughters. The haemophilia of Alexei would result in the rise to prominence of the Russian mystic [[Grigori Rasputin]] at the imperial court.<ref>{{cite book|last=Massie|first=Robert K.|title=Nicholas and Alexandra: The Classic Account of the Fall of the Romanov Dynasty
|publisher=[[Random House]]|date=2011|page=532|isbn=978-0-307-78847-4}}</ref>

It was claimed that Rasputin was successful at treating Tsarevich Alexei's haemophilia. At the time, a common treatment administered by professional doctors was to use [[aspirin]], which worsened rather than lessened the problem. It is believed that, by simply advising against the medical treatment, Rasputin could bring visible and significant improvement to the condition of Tsarevich Alexei.<ref>{{cite book|last=Jeffreys|first=Diarmud|title=Aspirin: The Remarkable Story of a Wonder Drug|publisher=[[Bloomsbury Publishing]]|date=2008|page=121|isbn=978-1-59691-816-0}}</ref>

In Spain, Queen Victoria's youngest daughter, [[Princess Beatrice of the United Kingdom|Princess Beatrice]], had a daughter [[Victoria Eugenie of Battenberg]], who later became Queen of Spain. Two of her sons were haemophiliacs and both died from minor car accidents. Her eldest son, [[Alfonso, Prince of Asturias (1907–1938)|Prince Alfonso of Spain, Prince of Asturias]], died at the age of 31 from internal bleeding after his car hit a telephone booth.<ref>{{Cite web|title=Tragic Drama Under the Miami Moon|url=http://www.biscaynetimes.com/index.php?option=com_content&id=264:tragic-drama-under-the-miami-moon&Itemid=162|access-date=24 June 2020|work=Biscayne times |archive-date=25 June 2020|archive-url=https://web.archive.org/web/20200625034408/http://www.biscaynetimes.com/index.php?option=com_content&id=264:tragic-drama-under-the-miami-moon&Itemid=162 |url-status=dead}}</ref> Her youngest son, [[Infante Gonzalo of Spain|Infante Gonzalo]], died at age 19 from abdominal bleeding following a minor car accident in which he and his sister hit a wall while avoiding a cyclist. Neither appeared injured or sought immediate medical care and Gonzalo died two days later from internal bleeding.<ref>{{Cite news|title=AUTO CRASH FATAL TO SPANISH PRINCE; Don Gonzalo, 19, Succumbs to Hemophilia After Collision in Austrian Village. INFANTA BEATRIZ DRIVING Swerved Car to Avoid Hitting Bicyclist – Ex-King Present at Son's Bedside.| work=The New York Times |url=http://timesmachine.nytimes.com/timesmachine/1934/08/14/93638215.html |access-date=24 June 2020|language=en}}</ref>

===Treatment===
The method for the production of an antihaemophilic factor was discovered by Judith Graham Pool from [[Stanford University]] in 1964,<ref>{{Cite journal|last1=Pool|first1=Judith G.|last2=Hershgold|first2=Edwabd J.|last3=Pappenhagen|first3=Albert R.|date=July 1964|title=High-potency Antihæmophilic Factor Concentrate prepared from Cryoglobulin Precipitate|journal=Nature|volume=203|issue=4942|pages=312|doi=10.1038/203312a0|pmid=14201780|issn=0028-0836|bibcode=1964Natur.203..312P|s2cid=4243913|doi-access=free}}</ref> and approved for commercial use in 1971 in the United States under the name ''[[Cryoprecipitate|Cryoprecipitated AHF]]''.<ref>{{Cite web|url=https://www.fda.gov/media/76356/download|title=Alphabetical List of Licensed Establishments Including Product Approval Dates as of 30-APR-2019|publisher=FDA}}</ref> Together with the development of a system for transportation and storage of human plasma in 1965, this was the first time an efficient treatment for haemophilia became available.<ref>{{Cite journal|last1=Pool|first1=Judith Graham|last2=Shannon|first2=Angela E.|date=30 December 1965|title=Production of High-Potency Concentrates of Antihemophilic Globulin in a Closed-Bag System: Assay in Vitro and in Vivo|journal=The New England Journal of Medicine|volume=273|issue=27|pages=1443–7|doi=10.1056/NEJM196512302732701|pmid=5852902|issn=0028-4793}}</ref>

===Blood contamination===
{{main|Contaminated haemophilia blood products}}
[[File:Ryan White.jpg|right|thumb|[[Ryan White]] was an American haemophiliac who became infected with [[HIV/AIDS]] through [[Contaminated haemophilia blood products|contaminated blood products]].]]

Up until late 1985 many people with haemophilia received clotting factor products that posed a risk of [[HIV]] and [[hepatitis C]] infection. The plasma used to create the products was not screened or tested, nor had most of the products been subject to any form of viral inactivation.{{Citation needed|date=July 2022}}

Tens of thousands worldwide were infected as a result of contaminated factor products including more than 10,000 people in the United States,<ref name="pmid20697550">{{cite journal | vauthors = White GC | title = Hemophilia: an amazing 35-year journey from the depths of HIV to the threshold of cure | journal = Trans. Am. Clin. Climatol. Assoc. | volume = 121 | pages = 61–73; discussion 74–5 | date = 2010 | pmid = 20697550 | pmc = 2917149 }}</ref> 3,500 British, 1,400 Japanese,<ref>{{cite web|url=http://www.jcie.org/researchpdfs/JapanResponseAIDS/Japansurvey.pdf|title=Japan's Response to the Spread of HIV/AIDS|publisher = Japan Center for International Exchange|year = 2004}}</ref> 700 Canadians,<ref>{{cite web|title=Commemoration of the Tainted Blood Tragedy – Canadian Hemophilia Society|url=http://www.hemophilia.ca/en/commemoration-of-the-tainted-blood-tragedy/|website=www.hemophilia.ca|date=17 October 2017 }}</ref> 250 Irish,<ref>{{cite web|title=Report of the Tribunal of Inquiry into the Infection with HIV and Hepatitis C of Persons with Haemophilia and Related Matters {{!}} Department of Health|url=http://health.gov.ie/blog/publications/report-of-the-tribunal-of-inquiry-into-the-infection-with-hiv-and-hepatitis-c-of-persons-with-haemophilia-and-related-matters/|website=health.gov.ie|date=30 September 2002 }}</ref> and 115 Iraqis.<ref>{{cite news|last1=Zielbauer|first1=Paul von|title=Iraqis Infected by H.I.V.-Tainted Blood Try New Tool: A Lawsuit|url=https://www.nytimes.com/2006/09/04/world/middleeast/04aids.html|newspaper=The New York Times|date=4 September 2006}}</ref>

Infection via the tainted factor products had mostly stopped by 1986 by which time viral inactivation methods had largely been put into place,<ref name="pmid3672104">{{cite journal | vauthors = Lowe GD | title = Haemophilia, blood products and HIV infection | journal = Scott Med J | volume = 32 | issue = 4 | pages = 109–11 | date = August 1987 | pmid = 3672104 | doi = 10.1177/003693308703200404| s2cid = 21773694 }}</ref> although some products were shown to still be dangerous in 1987.<ref>{{cite news|vauthors = Picard A|title=RCMP lay 32 charges in tainted-blood case |url=https://www.theglobeandmail.com/news/national/rcmp-lay-32-charges-in-tainted-blood-case/article25426655/| website = The Globe and Mail}}</ref>