Difference between revisions of "Timeline of hemophilia"

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This is a '''timeline of {{w|hemophilia}}''', describing important events in the development of the field.
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This is a '''timeline of {{w|hemophilia}}''', an inherited bleeding disorder that affects the blood's ability to clot.
  
 
==Big picture==
 
==Big picture==
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| 20th century || Until the early 1900s, there is no way to store blood for hemophiliacs so they are generally given a transfusion from a family member if they have suffered a trauma. At this point, the life expectancy for boys with hemophilia is around 13 years old. Some of the early treatments include lime, bone marrow, oxygen, thyroid gland, hydrogen peroxide or gelatin. In the 1930s, snake venom is used to help blood clotting. Hospital-based plasma transfusions are common treatments for hemophiliacs in the late 1920s and continue until the 1950s. The different factor deficiencies are distinguished in the 1950s and 1960s. By 1960, the life expectancy of a person with severe hemophilia rises to just under 20 years old. By the 1970s, freeze-dried powder formulas of factor VIII and IX become readily available, which means hemophiliacs are able to self-administer the factor in their own homes. In the 1980s, the rise of {{w|HIV}} and {{w|AIDS}} leads to many people with hemophilia dying of AIDS and becoming HIV positive through contaminated blood products. Hemophiliacs are also at a high risk of contracting {{w|hepatitis C}} until blood screening is introduced in 1992.<ref name="A Brief History of Hemophilia Treatment"/> In the 1990s, modern treatment, using safer factor concentrates, again improves the outlook of hemophilia.<ref name="History of hemophiliav"/>  
 
| 20th century || Until the early 1900s, there is no way to store blood for hemophiliacs so they are generally given a transfusion from a family member if they have suffered a trauma. At this point, the life expectancy for boys with hemophilia is around 13 years old. Some of the early treatments include lime, bone marrow, oxygen, thyroid gland, hydrogen peroxide or gelatin. In the 1930s, snake venom is used to help blood clotting. Hospital-based plasma transfusions are common treatments for hemophiliacs in the late 1920s and continue until the 1950s. The different factor deficiencies are distinguished in the 1950s and 1960s. By 1960, the life expectancy of a person with severe hemophilia rises to just under 20 years old. By the 1970s, freeze-dried powder formulas of factor VIII and IX become readily available, which means hemophiliacs are able to self-administer the factor in their own homes. In the 1980s, the rise of {{w|HIV}} and {{w|AIDS}} leads to many people with hemophilia dying of AIDS and becoming HIV positive through contaminated blood products. Hemophiliacs are also at a high risk of contracting {{w|hepatitis C}} until blood screening is introduced in 1992.<ref name="A Brief History of Hemophilia Treatment"/> In the 1990s, modern treatment, using safer factor concentrates, again improves the outlook of hemophilia.<ref name="History of hemophiliav"/>  
 
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| 21st century || New recombinant factors not containing contain human or animal plasma are introduced in the early 2000s, lessening the chance of allergic reactions. Currently, researchers are working on ways of correcting the mutated gene using viruses as vehicles to deliver corrected factor IX genes.<ref name="A Brief History of Hemophilia Treatment"/>
+
| 21st century || Recent advances include a better understanding of the cause, detection, and elimination of inhibitor antibodies found in many hemophilia patients.<ref name="Milestones in Hemophilia">{{cite web |title=Milestones in Hemophilia |url=http://www.hematology.org/About/History/50-Years/1513.aspx |website=hematology.org |accessdate=3 January 2019}}</ref> New recombinant factors not containing contain human or animal plasma are introduced in the early 2000s, lessening the chance of allergic reactions. Currently, researchers are working on ways of correcting the mutated gene using viruses as vehicles to deliver corrected factor IX genes.<ref name="A Brief History of Hemophilia Treatment"/>
 
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|-
 
|}
 
|}
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==Full timeline==
 
==Full timeline==
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| 1828 || Field development || Friedrich Hopff at the {{w|University of Zurich}} writes the word ''hemophilia'' in a description of the condition.<ref name="A Brief History of Hemophilia Treatment"/><ref name="History of hemophiliav"/><ref name="Encyclopedia of Lifestyle Medicine and Health"/> || {{w|Switzerland}}
 
| 1828 || Field development || Friedrich Hopff at the {{w|University of Zurich}} writes the word ''hemophilia'' in a description of the condition.<ref name="A Brief History of Hemophilia Treatment"/><ref name="History of hemophiliav"/><ref name="Encyclopedia of Lifestyle Medicine and Health"/> || {{w|Switzerland}}
 
|-
 
|-
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| 1840 || Treatment || The first successful blood transfusion in a hemophilic boy is conducted.<ref name="Production of Plasma Proteins for Therapeutic Use"/> ||
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| 1840 || Treatment || The first successful blood transfusion in a hemophilic boy is conducted.<ref>{{cite book |last1=Sebastian |first1=Anton |title=A Dictionary of the History of Medicine |url=https://books.google.com.ar/books?id=CvpKDwAAQBAJ&pg=PT929&dq=1840+The+first+successful+blood+transfusion+in+a+hemophilic+boy&hl=en&sa=X&ved=0ahUKEwi6peOag9LfAhUEj5AKHQvMD7QQ6AEIODAC#v=onepage&q=1840%20The%20first%20successful%20blood%20transfusion%20in%20a%20hemophilic%20boy&f=false}}</ref><ref>{{cite book |last1=Green |first1=David |title=Hemophilia and Von Willebrand Disease: Factor VIII and Von Willebrand Factor |url=https://books.google.com.ar/books?id=h11gDwAAQBAJ&pg=PA81&dq=1840+The+first+successful+blood+transfusion+in+a+hemophilic+boy&hl=en&sa=X&ved=0ahUKEwi6peOag9LfAhUEj5AKHQvMD7QQ6AEIPjAD#v=onepage&q=1840%20The%20first%20successful%20blood%20transfusion%20in%20a%20hemophilic%20boy&f=false}}</ref> ||
 
|-
 
|-
 
| 1901 || Treatment || The United States Surgeon General’s Catalogue lists lime, inhales oxygen and the use of thyroid gland or bone marrow, or hydrogen peroxide or gelatin, as treatments for hemophilia.<ref name="HISTORY OF BLEEDING DISORDERS"/> || {{w|United States}}
 
| 1901 || Treatment || The United States Surgeon General’s Catalogue lists lime, inhales oxygen and the use of thyroid gland or bone marrow, or hydrogen peroxide or gelatin, as treatments for hemophilia.<ref name="HISTORY OF BLEEDING DISORDERS"/> || {{w|United States}}
 
|-
 
|-
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| 1920 || Field development || {{w|Factor I deficiency}} is first described.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
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| 1920 || Field development || {{w|Factor I deficiency}} is first described.<ref name="HISTORY OF BLEEDING DISORDERS"/><ref>{{cite web |title=Factor I |url=https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Other-Factor-Deficiencies/Factor-I |website=hemophilia.org |accessdate=3 January 2019}}</ref> ||
 
|-
 
|-
 
| 1925–1930 || Treatment || Hospital-based plasma transfusions become common treatments for hemophiliacs.<ref name="A Brief History of Hemophilia Treatment"/> ||
 
| 1925–1930 || Treatment || Hospital-based plasma transfusions become common treatments for hemophiliacs.<ref name="A Brief History of Hemophilia Treatment"/> ||
 
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|-
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| 1926 || Field development || Finnish physician {{w|Erik von Willebrand}} publishes a paper describing what he calls “pseudohemophilia”, a bleeding disorder affecting men and women equally. It would later named {w|Von Willebrand disease}}.<ref name="HISTORY OF BLEEDING DISORDERS">{{cite web |title=HISTORY OF BLEEDING DISORDERS |url=https://hawaiinhf.org/bleeding-disorders/what-is-a-bleeding-disorder/history-of-bleeding-disorders.html |website=hawaiinhf.org |accessdate=22 October 2018}}</ref> ||
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| 1926 || Field development || Finnish physician {{w|Erik von Willebrand}} publishes a paper describing what he calls “pseudohemophilia”, a bleeding disorder affecting men and women equally. It would later named {{w|Von Willebrand disease}}.<ref name="HISTORY OF BLEEDING DISORDERS">{{cite web |title=HISTORY OF BLEEDING DISORDERS |url=https://hawaiinhf.org/bleeding-disorders/what-is-a-bleeding-disorder/history-of-bleeding-disorders.html |website=hawaiinhf.org |accessdate=22 October 2018}}</ref><ref>{{cite book |last1=Dorgalaleh |first1=Akbar |title=Congenital Bleeding Disorders: Diagnosis and Management |url=https://books.google.com.ar/books?id=411mDwAAQBAJ&pg=PA67&dq=1926+Erik+von+Willebrand++%E2%80%9Cpseudohemophilia%E2%80%9D&hl=en&sa=X&ved=0ahUKEwjboaLXgtLfAhVHlJAKHWFvCWkQ6AEIKjAA#v=onepage&q=1926%20Erik%20von%20Willebrand%20%20%E2%80%9Cpseudohemophilia%E2%80%9D&f=false}}</ref><ref>{{cite book |last1=Rajendran |first1=By R. |title=Shafer'S Textbook Of Oral Pathology (6Th Edition) |url=https://books.google.com.ar/books?id=Spk0V6TrCggC&pg=PA786&dq=1926+Erik+von+Willebrand++%E2%80%9Cpseudohemophilia%E2%80%9D&hl=en&sa=X&ved=0ahUKEwjboaLXgtLfAhVHlJAKHWFvCWkQ6AEILzAB#v=onepage&q=1926%20Erik%20von%20Willebrand%20%20%E2%80%9Cpseudohemophilia%E2%80%9D&f=false}}</ref> ||
 
|-
 
|-
 
| 1930 || Field development || Scientists learn how to separate blood into its major parts, plasma and red cells.<ref name="The History of Hemophilia">{{cite web |title=The History of Hemophilia |url=https://www.hog.org/handbook/article/1/3/the-history-of-hemophilia |website=hog.org |accessdate=22 October 2018}}</ref> ||
 
| 1930 || Field development || Scientists learn how to separate blood into its major parts, plasma and red cells.<ref name="The History of Hemophilia">{{cite web |title=The History of Hemophilia |url=https://www.hog.org/handbook/article/1/3/the-history-of-hemophilia |website=hog.org |accessdate=22 October 2018}}</ref> ||
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| 1936 || Treatment || The first plasma treatment for hemophilia is conducted.<ref name="Production of Plasma Proteins for Therapeutic Use"/> ||
 
| 1936 || Treatment || The first plasma treatment for hemophilia is conducted.<ref name="Production of Plasma Proteins for Therapeutic Use"/> ||
 
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|-
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| 1937 || Treatment || Drs Patek and Taylor, at {{w|Harvard}}, find they could correct the clotting problem by adding a substance coming from the plasma in blood. This is called anti-hemophilic globulin.<ref name="History of hemophiliav"/> || {{w|United States}}
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| 1937 || Treatment || Drs Patek and Taylor, at {{w|Harvard}}, find they could correct the clotting problem by adding a substance coming from the plasma in blood. This is called anti-hemophilic globulin.<ref name="History of hemophiliav"/><ref>{{cite book |last1=Pope |first1=Thomas |last2=Bloem |first2=Hans L. |last3=Beltran |first3=Javier |last4=Morrison |first4=William B. |last5=Wilson |first5=David John |title=Musculoskeletal Imaging |url=https://books.google.com.ar/books?id=GfITBQAAQBAJ&pg=PA870-IA1&lpg=PA870-IA1&dq=1937+Drs+Patek+and+Taylor,+at+Harvard&source=bl&ots=Om0e6As8Q-&sig=hd5q5yJr65xAbo1bopU3hacHJJc&hl=en&sa=X&ved=2ahUKEwiyvfvKhNLfAhUBEpAKHXtiDwYQ6AEwB3oECAgQAQ#v=onepage&q=1937%20Drs%20Patek%20and%20Taylor%2C%20at%20Harvard&f=false}}</ref> || {{w|United States}}
 
|-
 
|-
 
| 1930s || Field development || Doctors look at defective platelets as the likely cause of hemophilia.<ref name="History of hemophiliav"/> ||
 
| 1930s || Field development || Doctors look at defective platelets as the likely cause of hemophilia.<ref name="History of hemophiliav"/> ||
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| 1948 || Organization || The U.S. {{w|National Hemophilia Foundation}} (NHF) opens as The Hemophilia Foundation, Inc.<ref name="HISTORY OF BLEEDING DISORDERS"/> || {{w|United States}}
 
| 1948 || Organization || The U.S. {{w|National Hemophilia Foundation}} (NHF) opens as The Hemophilia Foundation, Inc.<ref name="HISTORY OF BLEEDING DISORDERS"/> || {{w|United States}}
 
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|-
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| 1940s || || Factors II and V deficiency are identified.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
+
| 1940s || Field development || Factors [[w:factor II|II]] and [[w:factor V|V]] deficiency are identified.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
|-
 
|-
 
| 1940s || Treatment || Whole blood transfusions start being given at hospitals.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
| 1940s || Treatment || Whole blood transfusions start being given at hospitals.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
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| 1955 || Treatment || The first infusions of {{w|factor VIII}} in plasma form are performed.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
| 1955 || Treatment || The first infusions of {{w|factor VIII}} in plasma form are performed.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
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|-
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| 1957 || Field development || Researchers in Sweden identify {{w|Von Willebrand factor}} as the cause of {{w|Von Willebrand disease}}.<ref name="HISTORY OF BLEEDING DISORDERS"/> || {{w|Sweden}}
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| 1957 || Field development || Researchers in Sweden identify {{w|Von Willebrand factor}} as the cause of {{w|Von Willebrand disease}}.<ref>{{cite journal |title=Scientific visits to the Aland Islands. |pmid=23401895 |url=https://www.ncbi.nlm.nih.gov/m/pubmed/23401895/}}</ref><ref>{{cite web |title=Von Willebrand's Disease–History, Diagnosis and Management |url=https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0028-1086116.pdf |website=thieme-connect.com |accessdate=3 January 2019}}</ref><ref name="HISTORY OF BLEEDING DISORDERS"/> || {{w|Sweden}}
 
|-
 
|-
 
| 1958 || Treatment || {{w|Prophylaxis}} for {{w|hemophilia A}} is first used.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
| 1958 || Treatment || {{w|Prophylaxis}} for {{w|hemophilia A}} is first used.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
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| 1955–1965 || Treatment || Hemophiliacs are treated with whole blood or fresh plasma.<ref name="History of hemophiliav"/> ||
 
| 1955–1965 || Treatment || Hemophiliacs are treated with whole blood or fresh plasma.<ref name="History of hemophiliav"/> ||
 
|-
 
|-
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| 1960s || || The clotting factors are identified and named.<ref name="History of hemophiliav"/> ||
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| 1960s || Field development || The clotting factors are identified and named.<ref name="History of hemophiliav"/> ||
 
|-
 
|-
 
| 1960 || || The life expectancy of a person with severe hemophilia rises to just under 20 years old.<ref name="A Brief History of Hemophilia Treatment"/> ||
 
| 1960 || || The life expectancy of a person with severe hemophilia rises to just under 20 years old.<ref name="A Brief History of Hemophilia Treatment"/> ||
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|-
 
| 1964 || Field development || An article published in ''[[w:Nature (journal)|Nature]]'' describes the clotting process in detail. The interaction of the different factors in blood clotting is named coagulation cascade.<ref name="History of hemophiliav"/> ||
 
| 1964 || Field development || An article published in ''[[w:Nature (journal)|Nature]]'' describes the clotting process in detail. The interaction of the different factors in blood clotting is named coagulation cascade.<ref name="History of hemophiliav"/> ||
 +
|-
 +
| 1964 || Field development || American physiologist {{w|Judith Graham Pool}} discovers a simple way to make cryoprecipitates (cold insoluable precipitates that contain factor VIII) for the treatment of hemophilia.<ref>{{cite book |last1=Sicherman |first1=Barbara |last2=Green |first2=Carol Hurd |title=Notable American Women: The Modern Period : a Biographical Dictionary |url=https://books.google.com.ar/books?id=CfGHM9KU7aEC&pg=PA553&dq=1964+Judith+Pool+cryoprecipitates&hl=en&sa=X&ved=0ahUKEwiFlerDidLfAhUJGJAKHXelAZEQ6AEIKjAA#v=onepage&q=1964%20Judith%20Pool%20cryoprecipitates&f=false}}</ref><ref>{{cite book |last1=Forbes |first1=C.D. |title=Unresolved problems in Haemophilia |url=https://books.google.com.ar/books?id=3GmSBAAAQBAJ&pg=PA75&dq=1964+Judith+Pool+cryoprecipitates&hl=en&sa=X&ved=0ahUKEwiFlerDidLfAhUJGJAKHXelAZEQ6AEINTAC#v=onepage&q=1964%20Judith%20Pool%20cryoprecipitates&f=false}}</ref><ref>{{cite book |title=Textbook of Hemophilia |edition=Christine A. Lee, Erik E. Berntorp, W. Keith Hoots |url=https://books.google.com.ar/books?id=DkvmZbofLPQC&pg=PT319&dq=1964+Judith+Pool+cryoprecipitates&hl=en&sa=X&ved=0ahUKEwiFlerDidLfAhUJGJAKHXelAZEQ6AEIOzAD#v=onepage&q=1964%20Judith%20Pool%20cryoprecipitates&f=false}}</ref> || {{w|United States}}
 
|-
 
|-
 
| 1965 || Field development || Dr. Judith Graham Pool from Stanford University discovers a process of freezing and thawing plasma to get a layer of factor-rich plasma ({{w|cryoprecipitate}}).<ref name="The History of Hemophilia"/> Graham Pool discovers that the cryoprecipitate left from thawing plasma is high in factor VIII. This could be infused to control heavy bleeding allowing blood banks to produce and store large amounts for use in surgical procedures for hemophiliacs.<ref name="A Brief History of Hemophilia Treatment"/> || {{w|United States}}
 
| 1965 || Field development || Dr. Judith Graham Pool from Stanford University discovers a process of freezing and thawing plasma to get a layer of factor-rich plasma ({{w|cryoprecipitate}}).<ref name="The History of Hemophilia"/> Graham Pool discovers that the cryoprecipitate left from thawing plasma is high in factor VIII. This could be infused to control heavy bleeding allowing blood banks to produce and store large amounts for use in surgical procedures for hemophiliacs.<ref name="A Brief History of Hemophilia Treatment"/> || {{w|United States}}
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| 1965–1975 || Treatment || Concentrates containing {{w|factor IX}} begin to be available.<ref name="History of hemophiliav"/> ||
 
| 1965–1975 || Treatment || Concentrates containing {{w|factor IX}} begin to be available.<ref name="History of hemophiliav"/> ||
 
|-
 
|-
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| 1974 || Literature (book) || ''Living with Haemophilia'', by Peter Jones, is published.<ref>{{cite web |title=Living with Haemophilia |url=https://www.google.com/search?client=ubuntu&sa=X&channel=fs&q=Living+with+Haemophilia&stick=H4sIAAAAAAAAAGVTu47UMBQlBWjXO0hLRjSpVoiCAimvyYsWIYTECgm2oIvWcZzMxHYetuKxP2M7alp-hPkASgo6_oASdtnEkaY8Pveee8-91ycPnwGXul5Mq5yqYA3btuEXLbuoS9p29ZZsrw_Wyq1cP4BUizDN7qG_ifadl6cz2_FwhOxgLeQO1uO70GLQFRv8YMJo30gZ1b5RjmOR7iflUPfVsMsNm1ReSudkHGOMuEkWSCbaM9FFPmbyYJ3e9oEQ5XtDpTDr0SRU4WiEo1x0kdbDYMqybpf4ajLUNDTWhiuGpo8WNdNKD3P_qs404YbNCz0iA7kneDjPJgpwlW3GGfuM7rwgNHMlsFHIuJc6KHSwGM6QqUWtTBbSOO58CXdTsE9l75Gc3FsKEuglE9jIoG6m7SVRRUQzlcRaCcGT4hhPNXGufHhs4D-GSY_1Rho-CusRi8XCsoRE81mF477rdbzITnEaLJaUhTtlxCOidc7M0jpPN3JxOtUmZ9isjYUENTPkBKuin082l4j9sr5aZ-e___xcO1-sm2_ff1g3Fjh_37a8JOpjSa5Fia5a-zl49IaJrVC2A1bOyW1-SNXw4oEDwIzsz-DsUymu2ssWbbGy39lvwellSWE58A_YfgXA65aQshDbltkvwVPniVvMD-7dT_wnuAbHz6u_YARTH7cDAAA&npsic=0&ved=0ahUKEwjPxYWT2d7eAhXO-qQKHZOkCTMQ-BYIQQ |accessdate=18 November 2018}}</ref> ||
+
| 1970s || Treatment || Primary prophylaxis therapy experiments begin.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
|-
 
|-
−
| 1977 || Treatment || {{w|Desmopressin}} is identified to treat mild hemophilia and {{w|von Willebrand disease}}.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
+
| 1970s || Treatment || Freeze-dried plasma-derived factor concentrates become available.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
|-
 
|-
−
| 1970s || Treatment || Primary prophylaxis therapy experiments begin.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
+
| 1974 || Literature (book) || ''Living with Haemophilia'', by Peter Jones, is published.<ref>{{cite web |title=Living with Haemophilia |url=https://www.google.com/search?client=ubuntu&sa=X&channel=fs&q=Living+with+Haemophilia&stick=H4sIAAAAAAAAAGVTu47UMBQlBWjXO0hLRjSpVoiCAimvyYsWIYTECgm2oIvWcZzMxHYetuKxP2M7alp-hPkASgo6_oASdtnEkaY8Pveee8-91ycPnwGXul5Mq5yqYA3btuEXLbuoS9p29ZZsrw_Wyq1cP4BUizDN7qG_ifadl6cz2_FwhOxgLeQO1uO70GLQFRv8YMJo30gZ1b5RjmOR7iflUPfVsMsNm1ReSudkHGOMuEkWSCbaM9FFPmbyYJ3e9oEQ5XtDpTDr0SRU4WiEo1x0kdbDYMqybpf4ajLUNDTWhiuGpo8WNdNKD3P_qs404YbNCz0iA7kneDjPJgpwlW3GGfuM7rwgNHMlsFHIuJc6KHSwGM6QqUWtTBbSOO58CXdTsE9l75Gc3FsKEuglE9jIoG6m7SVRRUQzlcRaCcGT4hhPNXGufHhs4D-GSY_1Rho-CusRi8XCsoRE81mF477rdbzITnEaLJaUhTtlxCOidc7M0jpPN3JxOtUmZ9isjYUENTPkBKuin082l4j9sr5aZ-e___xcO1-sm2_ff1g3Fjh_37a8JOpjSa5Fia5a-zl49IaJrVC2A1bOyW1-SNXw4oEDwIzsz-DsUymu2ssWbbGy39lvwellSWE58A_YfgXA65aQshDbltkvwVPniVvMD-7dT_wnuAbHz6u_YARTH7cDAAA&npsic=0&ved=0ahUKEwjPxYWT2d7eAhXO-qQKHZOkCTMQ-BYIQQ |accessdate=18 November 2018}}</ref> ||
 
|-
 
|-
−
| 1970s || Treatment || Freeze-dried plasma-derived factor concentrates become available.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
+
| 1977 || Treatment || {{w|Desmopressin}} is identified to treat mild hemophilia and {{w|von Willebrand disease}}.<ref name="HISTORY OF BLEEDING DISORDERS"/><ref>{{cite journal |last1=Castaman |first1=G |title=Desmopressin for the treatment of haemophilia. |doi=10.1111/j.1365-2516.2007.01606.x |url=https://www.ncbi.nlm.nih.gov/pubmed/18173690}}</ref><ref>{{cite journal |last1=Federici |first1=AB |title=The use of desmopressin in von Willebrand disease: the experience of the first 30 years (1977-2007). |doi=10.1111/j.1365-2516.2007.01610.x |url=https://www.ncbi.nlm.nih.gov/pubmed/18173689}}</ref> ||
 
|-
 
|-
 
| 1982 || Field development || The United States {{w|Centers for Disease Control and Prevention}} reports first {{w|AIDS}} cases among people with hemophilia.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
| 1982 || Field development || The United States {{w|Centers for Disease Control and Prevention}} reports first {{w|AIDS}} cases among people with hemophilia.<ref name="HISTORY OF BLEEDING DISORDERS"/> ||
 
|-
 
|-
−
| 1984 || Treatment || First heat-treated {{w|factor VIII}} concentrates become available.<ref name="Production of Plasma Proteins for Therapeutic Use"/><ref name="Production of Plasma Proteins for Therapeutic Use">{{cite book |last1=Goss |first1=Neil |title=Production of Plasma Proteins for Therapeutic Use |url=https://books.google.com.ar/books?id=MGL0QOc-rtsC&pg=PA32&lpg=PA32&dq=1985++The+first+SD-treated+factor+VIII+concentrates&source=bl&ots=r6je45XzjW&sig=jReExLewz5-fXhgJ_BTX9Hy8o00&hl=en&sa=X&ved=2ahUKEwjk_ZDg89HfAhWDg5AKHbpZD4YQ6AEwDHoECAMQAQ#v=onepage&q=1985%20%20The%20first%20SD-treated%20factor%20VIII%20concentrates&f=false}}</ref> ||
+
| 1984 || Treatment || First heat-treated {{w|factor VIII}} concentrates become available.<ref name="Production of Plasma Proteins for Therapeutic Use"/><ref name="Production of Plasma Proteins for Therapeutic Use"/> ||
 
|-
 
|-
 
| 1985 || Treatment || The first inactivated factor concentrates become available.<ref name="HISTORY OF BLEEDING DISORDERS"/><ref>{{cite web |title=History of Bleeding Disorders |url=https://cohemo.org/bleeding-disorders/what-is-a-bleeding-disorder/history-of-bleeding-disorders.html |website=cohemo.org |accessdate=3 January 2019}}</ref> ||
 
| 1985 || Treatment || The first inactivated factor concentrates become available.<ref name="HISTORY OF BLEEDING DISORDERS"/><ref>{{cite web |title=History of Bleeding Disorders |url=https://cohemo.org/bleeding-disorders/what-is-a-bleeding-disorder/history-of-bleeding-disorders.html |website=cohemo.org |accessdate=3 January 2019}}</ref> ||
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| 1991 || Literature (book) || ''Raising a Child with Hemophilia: A Practical Guide for Parents'', by Laureen A. Kelley, is published.<ref>{{cite web |title=Raising a Child with Hemophilia: A Practical Guide for Parents |url=https://www.google.com/search?client=ubuntu&hs=m1&channel=fs&q=Raising+a+Child+with+Hemophilia:+A+Practical+Guide+for+Parents&stick=H4sIAAAAAAAAAGVTu27UQBTFBSiZLFLwimarCFFQIPm1ftEiFCERIUEKOiv2eOxdz8P2jDw78xnpqNPyI-wHUFLQ8QeUkCX2WNryzLn33Me5c_L4xcKpHM9bh7vWzRJ_mTPW8AtGL-qSsLbe4M3N3jrE-DnRIkjSBzimTGzLgyGnews4xHEjUmVE7a2nh9Ci1xXtPX_EcNdIGdaeUY4ikexG5UB3Vb_NDBtXbkKmZBQhBLlJFlDG2jXRRTakcm-d3vcBIeE7QyV52sFRqELhkA9y1kVS970pS9tt7KlxoKYhkTZc0TddOKuZVLqf-ld1qjE3bFboARrIXcGDaTehj6p0PUzYo2Tr-oHZK84bBc30UvuF9mfL6VM1q5XKQpqJW0_m2zHYI7JzcYYfRvLj3I1HsJZ-3YzuxWGFRTOWRFoJwePiGI81Uaa8_HiA_ziPO6TX0vBhUA9IzAxLYxxOZxUMu7bT0Sw7QYk_MykNtsqIh1jrjBrTWlc3cnY61TqjyNhGAwybCXKMVNFNJ5tJSH9Zd9bZ-e8_P5err9btt-8_rFsLnH9gjJdYfSrxjSjhNbNfgifvqNgIZa_AYnVynx8Q1b96tAJgQvYXcPa5FNfsisENUvZ7-xKcXpUkL3v-EdlvAHjLMC4LsWHUfg2er545xfTgHH7iP8ElOH5e_AX8vaFPuQMAAA&npsic=0&sa=X&ved=0ahUKEwipmtCe1t7eAhXS2KQKHb5ECo0Q-BYIOw |accessdate=18 November 2018}}</ref> ||
 
| 1991 || Literature (book) || ''Raising a Child with Hemophilia: A Practical Guide for Parents'', by Laureen A. Kelley, is published.<ref>{{cite web |title=Raising a Child with Hemophilia: A Practical Guide for Parents |url=https://www.google.com/search?client=ubuntu&hs=m1&channel=fs&q=Raising+a+Child+with+Hemophilia:+A+Practical+Guide+for+Parents&stick=H4sIAAAAAAAAAGVTu27UQBTFBSiZLFLwimarCFFQIPm1ftEiFCERIUEKOiv2eOxdz8P2jDw78xnpqNPyI-wHUFLQ8QeUkCX2WNryzLn33Me5c_L4xcKpHM9bh7vWzRJ_mTPW8AtGL-qSsLbe4M3N3jrE-DnRIkjSBzimTGzLgyGnews4xHEjUmVE7a2nh9Ci1xXtPX_EcNdIGdaeUY4ikexG5UB3Vb_NDBtXbkKmZBQhBLlJFlDG2jXRRTakcm-d3vcBIeE7QyV52sFRqELhkA9y1kVS970pS9tt7KlxoKYhkTZc0TddOKuZVLqf-ld1qjE3bFboARrIXcGDaTehj6p0PUzYo2Tr-oHZK84bBc30UvuF9mfL6VM1q5XKQpqJW0_m2zHYI7JzcYYfRvLj3I1HsJZ-3YzuxWGFRTOWRFoJwePiGI81Uaa8_HiA_ziPO6TX0vBhUA9IzAxLYxxOZxUMu7bT0Sw7QYk_MykNtsqIh1jrjBrTWlc3cnY61TqjyNhGAwybCXKMVNFNJ5tJSH9Zd9bZ-e8_P5err9btt-8_rFsLnH9gjJdYfSrxjSjhNbNfgifvqNgIZa_AYnVynx8Q1b96tAJgQvYXcPa5FNfsisENUvZ7-xKcXpUkL3v-EdlvAHjLMC4LsWHUfg2er545xfTgHH7iP8ElOH5e_AX8vaFPuQMAAA&npsic=0&sa=X&ved=0ahUKEwipmtCe1t7eAhXS2KQKHb5ECo0Q-BYIOw |accessdate=18 November 2018}}</ref> ||
 
|-
 
|-
−
| 1992 || Field development || Blood screening is introduced. Prior to this, hemophiliacs were at a high risk of contracting {{w|hepatitis C}} and other diseases.<ref name="A Brief History of Hemophilia Treatment"/> ||
+
| 1992 || Field development || Blood screening is introduced. Prior to this, hemophiliacs were at a high risk of contracting {{w|hepatitis C}} and other diseases.<ref name="A Brief History of Hemophilia Treatment"/><ref>{{cite web |title=Hepatitis C Transmission |url=https://hepatitisc.net/what-is/transmission/ |website=hepatitisc.net |accessdate=3 January 2019}}</ref><ref>{{cite journal |last1=Gupta |first1=Ekta |last2=Bajpai |first2=Meenu |last3=Choudhary |first3=Aashish |title=Hepatitis C virus: Screening, diagnosis, and interpretation of laboratory assays |doi=10.4103/0973-6247.126683 |pmid=24678168 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943138/}}</ref> ||
 
|-
 
|-
 
| 1992 || Treatment || The first recombinant {{w|factor VIII}} product is approved by the United States {{w|Food and Drug Administration}}.<ref name="HISTORY OF BLEEDING DISORDERS"/><ref name="A Brief History of Hemophilia Treatment"/><ref name="Production of Plasma Proteins for Therapeutic Use"/> || {{w|United States}}
 
| 1992 || Treatment || The first recombinant {{w|factor VIII}} product is approved by the United States {{w|Food and Drug Administration}}.<ref name="HISTORY OF BLEEDING DISORDERS"/><ref name="A Brief History of Hemophilia Treatment"/><ref name="Production of Plasma Proteins for Therapeutic Use"/> || {{w|United States}}
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|-
 
|-
 
|}
 
|}
 +
 +
== Numerical and visual data  ==
 +
 +
=== Google Scholar ===
 +
 +
The following table summarizes per-year mentions on Google Scholar as of June 8, 2021.
 +
 +
{| class="sortable wikitable"
 +
! Year
 +
! hemophilia
 +
! hemophilia prophylaxis
 +
! hemophilia treatment
 +
! hemophilia gene therapy
 +
|-
 +
| 1980 || 724 || 68 || 364 || 99
 +
|-
 +
| 1985 || 1,580 || 240 || 923 || 352
 +
|-
 +
| 1990 || 1,730 || 272 || 974 || 463
 +
|-
 +
| 1995 || 2,040 || 367 || 1,250 || 649
 +
|-
 +
| 2000 || 2,850  || 529 || 1,930 || 1,370
 +
|-
 +
| 2002 || 2,990 || 635 || 2,210 || 1,500
 +
|-
 +
| 2004 || 3,910 || 740 || 2,720 || 1,770
 +
|-
 +
| 2006 || 4,510 || 1,020 || 3,250 || 2,100
 +
|-
 +
| 2008 || 5,210 || 1,190 || 3,780 || 2,230
 +
|-
 +
| 2010 || 5,060 || 1,160 || 3,670 || 2,320
 +
|-
 +
| 2012 || 6,500 || 1,590 || 4,790 || 2,920
 +
|-
 +
| 2014 || 6,330 || 1,570 || 4,760 || 2,790
 +
|-
 +
| 2016 || 6,800 || 1,840 || 5,350 || 3,180 
 +
|-
 +
| 2017 || 6,700 || 1,700 || 5,290 || 3,100
 +
|-
 +
| 2018 || 6,930 || 2,010 || 5,470 || 3,170
 +
|-
 +
| 2019 || 7,000 || 1,970 || 5,640 || 3,390
 +
|-
 +
| 2020 || 7,900 || 2,180 || 5,920 || 3,500
 +
|-
 +
|}
 +
 +
 +
[[File:Hemophilia tb.png|thumb|center|700px]]
 +
 +
=== Google Trends ===
 +
The comparative chart below shows {{w|Google Trends}} data for Haemophilia (Genetic disorder) and Haemophilia (Search term) from January 2004 to February 2021, when the screenshot was taken. Interest is also ranked by country and displayed on world map. <ref>{{cite web |title=Haemophilia |url=https://trends.google.com/trends/explore?date=all&q=%2Fm%2F03myr,Hemophilia |website=Google Trends |access-date=25 February 2021}}</ref>
 +
 +
[[File:Haemophilia gt.png|thumb|center|600px]]
 +
 +
=== Google Ngram Viewer ===
 +
The chart below shows {{w|Google Ngram Viewer}} data for Hemophilia from 1700 to 2019.<ref>{{cite web |title=Hemophilia |url=https://books.google.com/ngrams/graph?content=Hemophilia&year_start=1700&year_end=2019&corpus=26&smoothing=3&case_insensitive=true |website=books.google.com |access-date=25 February 2021 |language=en}}</ref>
 +
 +
[[File:Haemophilia ngram.png|thumb|center|700px]]
 +
 +
=== Wikipedia Views ===
 +
The chart below shows pageviews of the English Wikipedia article {{w|Hemophilia}}, on desktop, mobile-web, desktop-spider, mobile-web-spider and mobile app, from July 2015 to January 2021.<ref>{{cite web |title=Hemophilia |url=https://wikipediaviews.org/displayviewsformultiplemonths.php?page=Hemophilia&allmonths=allmonths-api&language=en&drilldown=all |website=wikipediaviews.org |access-date=24 February 2021}}</ref>
 +
 +
[[File:Hemophilia wv.jpg|thumb|center|400px]]
 +
  
 
==Meta information on the timeline==
 
==Meta information on the timeline==

Latest revision as of 20:42, 12 March 2024

This is a timeline of hemophilia, an inherited bleeding disorder that affects the blood's ability to clot.

Big picture

Time period Development summary.
Ancient times Hemophilia is recognized, though not named.[1]
19th century While the history of hemophilia dates back to the 2nd century AD, a modern description of hemophilia appears only at the beginning of the 19th century.[2] Hemophilia figures prominently in the history of European royalty in the 19th and following century. Britain's Queen Victoria, through two of her five daughters (Princess Alice and Princess Beatrice), passes the mutation to various royal houses across the continent, including the royal families of Spain, Germany and Russia.[3]
20th century Until the early 1900s, there is no way to store blood for hemophiliacs so they are generally given a transfusion from a family member if they have suffered a trauma. At this point, the life expectancy for boys with hemophilia is around 13 years old. Some of the early treatments include lime, bone marrow, oxygen, thyroid gland, hydrogen peroxide or gelatin. In the 1930s, snake venom is used to help blood clotting. Hospital-based plasma transfusions are common treatments for hemophiliacs in the late 1920s and continue until the 1950s. The different factor deficiencies are distinguished in the 1950s and 1960s. By 1960, the life expectancy of a person with severe hemophilia rises to just under 20 years old. By the 1970s, freeze-dried powder formulas of factor VIII and IX become readily available, which means hemophiliacs are able to self-administer the factor in their own homes. In the 1980s, the rise of HIV and AIDS leads to many people with hemophilia dying of AIDS and becoming HIV positive through contaminated blood products. Hemophiliacs are also at a high risk of contracting hepatitis C until blood screening is introduced in 1992.[4] In the 1990s, modern treatment, using safer factor concentrates, again improves the outlook of hemophilia.[1]
21st century Recent advances include a better understanding of the cause, detection, and elimination of inhibitor antibodies found in many hemophilia patients.[5] New recombinant factors not containing contain human or animal plasma are introduced in the early 2000s, lessening the chance of allergic reactions. Currently, researchers are working on ways of correcting the mutated gene using viruses as vehicles to deliver corrected factor IX genes.[4]


Full timeline

Year Event type Details Location
2nd century AD Field development The first written reference to a bleeding disorder appears in the Babylonian Talmud.[6][1]
12th century Treatment Arab physician Albucasis authors the first written reference to hemophilia treatment.[1][6]
1803 Field development American physician John Conrad Otto from Philadelphia publishes a paper about a familial bleeding disorder that only affects male members.[4][1] United States
1828 Field development Friedrich Hopff at the University of Zurich writes the word hemophilia in a description of the condition.[4][1][7] Switzerland
1840 Treatment The first successful blood transfusion in a hemophilic boy is conducted.[8][9]
1901 Treatment The United States Surgeon General’s Catalogue lists lime, inhales oxygen and the use of thyroid gland or bone marrow, or hydrogen peroxide or gelatin, as treatments for hemophilia.[10] United States
1920 Field development Factor I deficiency is first described.[10][11]
1925–1930 Treatment Hospital-based plasma transfusions become common treatments for hemophiliacs.[4]
1926 Field development Finnish physician Erik von Willebrand publishes a paper describing what he calls “pseudohemophilia”, a bleeding disorder affecting men and women equally. It would later named Von Willebrand disease.[10][12][13]
1930 Field development Scientists learn how to separate blood into its major parts, plasma and red cells.[14]
1934 Treatment Snake venom is used to help blood clotting.[4][6]
1936 Treatment The first plasma treatment for hemophilia is conducted.[6]
1937 Treatment Drs Patek and Taylor, at Harvard, find they could correct the clotting problem by adding a substance coming from the plasma in blood. This is called anti-hemophilic globulin.[1][15] United States
1930s Field development Doctors look at defective platelets as the likely cause of hemophilia.[1]
1944 Field development Argentine physician Alfredo Pavlovsky shows in a lab test that blood from one hemophiliac could correct the clotting problem in a second hemophiliac and vice-versa.[16] Argentina
1946 Field development American biochemist Edwin Joseph Cohn describes the later called Cohn process, by which human plasma may be separated into five fractions.[6][17] United States
1947 Field development Alfredo Pavlovsky discovers two types of hemophilia (A and B).[4] Argentina
1948 Organization The U.S. National Hemophilia Foundation (NHF) opens as The Hemophilia Foundation, Inc.[10] United States
1940s Field development Factors II and V deficiency are identified.[10]
1940s Treatment Whole blood transfusions start being given at hospitals.[10]
1952 Field development Hemophilia A and hemophilia B are recognized as two distinct diseases.[1]
1952 Field development Factor IX is identified in a patient with hemophilia B.[10][7]
1955 Treatment The first infusions of factor VIII in plasma form are performed.[10]
1957 Field development Researchers in Sweden identify Von Willebrand factor as the cause of Von Willebrand disease.[18][19][10] Sweden
1958 Treatment Prophylaxis for hemophilia A is first used.[10]
1955–1965 Treatment Hemophiliacs are treated with whole blood or fresh plasma.[1]
1960s Field development The clotting factors are identified and named.[1]
1960 The life expectancy of a person with severe hemophilia rises to just under 20 years old.[4]
1961 Treatment Factor VIII concentrates are first used.[6]
1964 Field development An article published in Nature describes the clotting process in detail. The interaction of the different factors in blood clotting is named coagulation cascade.[1]
1964 Field development American physiologist Judith Graham Pool discovers a simple way to make cryoprecipitates (cold insoluable precipitates that contain factor VIII) for the treatment of hemophilia.[20][21][22] United States
1965 Field development Dr. Judith Graham Pool from Stanford University discovers a process of freezing and thawing plasma to get a layer of factor-rich plasma (cryoprecipitate).[14] Graham Pool discovers that the cryoprecipitate left from thawing plasma is high in factor VIII. This could be infused to control heavy bleeding allowing blood banks to produce and store large amounts for use in surgical procedures for hemophiliacs.[4] United States
1968 Treatment The first factor VIII concentrate becomes available.[10]
1965–1975 Treatment Concentrates containing factor IX begin to be available.[1]
1970s Treatment Primary prophylaxis therapy experiments begin.[10]
1970s Treatment Freeze-dried plasma-derived factor concentrates become available.[10]
1974 Literature (book) Living with Haemophilia, by Peter Jones, is published.[23]
1977 Treatment Desmopressin is identified to treat mild hemophilia and von Willebrand disease.[10][24][25]
1982 Field development The United States Centers for Disease Control and Prevention reports first AIDS cases among people with hemophilia.[10]
1984 Treatment First heat-treated factor VIII concentrates become available.[6][6]
1985 Treatment The first inactivated factor concentrates become available.[10][26]
1985 Treatment The first SD-treated factor VIII concentrates become available.[6][6]
1988 Treatment The first high purity factor VIII concentrates become available.[6][6]
1980s Field development Factor VIII, factor IX and von Willebrand factor genes are cloned.[10]
1991 Literature (book) Raising a Child with Hemophilia: A Practical Guide for Parents, by Laureen A. Kelley, is published.[27]
1992 Field development Blood screening is introduced. Prior to this, hemophiliacs were at a high risk of contracting hepatitis C and other diseases.[4][28][29]
1992 Treatment The first recombinant factor VIII product is approved by the United States Food and Drug Administration.[10][4][6] United States
1995 Treatment Prophylaxis starts being used as a preventive treatment for children.[10][4]
1997 Treatment The first recombinant factor IX product is approved by the United States Food and Drug Administration.[10] United States
1997 Treatment A bypassing agent is developed, offering patients an alternative product to help stop bleeds and joint damage.[10]
1998 Medical development First human gene therapy trials begin.[10]
2005 Literature (book) Textbook of Hemophilia, by Erik E. Berntorp, is published.[30]
2007 Literature (book) Haemophilia and Haemostasis: A Case-based Approach to Management, by Harold R. Roberts, is published.[31]
2008 Literature (book) Hemophilia, by Michelle Raabe, is published.[32]
2009 Treatment The United States Food and Drug Administration approves RiaSTAP to treat factor I deficiency.[10] United States
2011 Treatment The United States Food and Drug Administration approves Corifact to treat factor XIII deficiency.[10] United States
2011 Literature (book) The Bleeding Disease: Hemophilia and the Unintended Consequences of Medical Progress, by Stephen Pemberto, is published.[33]
2012 Literature (book) Hemophilia and Hemostasis: A Case-Based Approach to Management, by Harold R. Roberts, Miguel A. Escobar and Alice D. Ma, is published.[34]
2016 Literature (book) Hemophilia: The Royal Disease, by Todd Eckdahl, is published.[35]

Numerical and visual data

Google Scholar

The following table summarizes per-year mentions on Google Scholar as of June 8, 2021.

Year hemophilia hemophilia prophylaxis hemophilia treatment hemophilia gene therapy
1980 724 68 364 99
1985 1,580 240 923 352
1990 1,730 272 974 463
1995 2,040 367 1,250 649
2000 2,850 529 1,930 1,370
2002 2,990 635 2,210 1,500
2004 3,910 740 2,720 1,770
2006 4,510 1,020 3,250 2,100
2008 5,210 1,190 3,780 2,230
2010 5,060 1,160 3,670 2,320
2012 6,500 1,590 4,790 2,920
2014 6,330 1,570 4,760 2,790
2016 6,800 1,840 5,350 3,180
2017 6,700 1,700 5,290 3,100
2018 6,930 2,010 5,470 3,170
2019 7,000 1,970 5,640 3,390
2020 7,900 2,180 5,920 3,500


Hemophilia tb.png

Google Trends

The comparative chart below shows Google Trends data for Haemophilia (Genetic disorder) and Haemophilia (Search term) from January 2004 to February 2021, when the screenshot was taken. Interest is also ranked by country and displayed on world map. [36]

Haemophilia gt.png

Google Ngram Viewer

The chart below shows Google Ngram Viewer data for Hemophilia from 1700 to 2019.[37]

Haemophilia ngram.png

Wikipedia Views

The chart below shows pageviews of the English Wikipedia article Hemophilia, on desktop, mobile-web, desktop-spider, mobile-web-spider and mobile app, from July 2015 to January 2021.[38]

Hemophilia wv.jpg


Meta information on the timeline

How the timeline was built

The initial version of the timeline was written by User:Sebastian.

Funding information for this timeline is available.

Feedback and comments

Feedback for the timeline can be provided at the following places:

  • FIXME

What the timeline is still missing

Timeline update strategy

See also

External links

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 "History of hemophilia". hemophilia.ca. Retrieved 22 October 2018. 
  2. ↑ Franchini, M; Mannucci, PM. "The history of hemophilia.". PMID 24911674. doi:10.1055/s-0034-1381232. 
  3. ↑ "Hemophilia: "The Royal Disease"". hemophiliaprince.com. Retrieved 22 October 2018. 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 "A Brief History of Hemophilia Treatment". hemophilianewstoday.com. Retrieved 22 October 2018. 
  5. ↑ "Milestones in Hemophilia". hematology.org. Retrieved 3 January 2019. 
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 Goss, Neil. Production of Plasma Proteins for Therapeutic Use. 
  7. ↑ 7.0 7.1 Rippe, James M. Encyclopedia of Lifestyle Medicine and Health. 
  8. ↑ Sebastian, Anton. A Dictionary of the History of Medicine. 
  9. ↑ Green, David. Hemophilia and Von Willebrand Disease: Factor VIII and Von Willebrand Factor. 
  10. ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 10.13 10.14 10.15 10.16 10.17 10.18 10.19 10.20 10.21 10.22 10.23 "HISTORY OF BLEEDING DISORDERS". hawaiinhf.org. Retrieved 22 October 2018. 
  11. ↑ "Factor I". hemophilia.org. Retrieved 3 January 2019. 
  12. ↑ Dorgalaleh, Akbar. Congenital Bleeding Disorders: Diagnosis and Management. 
  13. ↑ Rajendran, By R. Shafer'S Textbook Of Oral Pathology (6Th Edition). 
  14. ↑ 14.0 14.1 "The History of Hemophilia". hog.org. Retrieved 22 October 2018. 
  15. ↑ Pope, Thomas; Bloem, Hans L.; Beltran, Javier; Morrison, William B.; Wilson, David John. Musculoskeletal Imaging. 
  16. ↑ Hougie, Cecil. Thrombosis and Bleeding: An Era of Discovery. 
  17. ↑ Johnston, Anna; Adcock, Wayne. "The Use of Chromatography to Manufacture Purer and Safer Plasma Products". doi:10.1080/02648725.2000.10647987. 
  18. ↑ "Scientific visits to the Aland Islands.". PMID 23401895. 
  19. ↑ "Von Willebrand's Disease–History, Diagnosis and Management" (PDF). thieme-connect.com. Retrieved 3 January 2019. 
  20. ↑ Sicherman, Barbara; Green, Carol Hurd. Notable American Women: The Modern Period : a Biographical Dictionary. 
  21. ↑ Forbes, C.D. Unresolved problems in Haemophilia. 
  22. ↑ Textbook of Hemophilia (Christine A. Lee, Erik E. Berntorp, W. Keith Hoots ed.). 
  23. ↑ "Living with Haemophilia". Retrieved 18 November 2018. 
  24. ↑ Castaman, G. "Desmopressin for the treatment of haemophilia.". doi:10.1111/j.1365-2516.2007.01606.x. 
  25. ↑ Federici, AB. "The use of desmopressin in von Willebrand disease: the experience of the first 30 years (1977-2007).". doi:10.1111/j.1365-2516.2007.01610.x. 
  26. ↑ "History of Bleeding Disorders". cohemo.org. Retrieved 3 January 2019. 
  27. ↑ "Raising a Child with Hemophilia: A Practical Guide for Parents". Retrieved 18 November 2018. 
  28. ↑ "Hepatitis C Transmission". hepatitisc.net. Retrieved 3 January 2019. 
  29. ↑ Gupta, Ekta; Bajpai, Meenu; Choudhary, Aashish. "Hepatitis C virus: Screening, diagnosis, and interpretation of laboratory assays". PMID 24678168. doi:10.4103/0973-6247.126683. 
  30. ↑ "Textbook of Hemophilia". Retrieved 18 November 2018. 
  31. ↑ "Haemophilia and Haemostasis: A Case-based Approach to Management". Retrieved 18 November 2018. 
  32. ↑ "Hemophilia". Retrieved 18 November 2018. 
  33. ↑ "The Bleeding Disease: Hemophilia and the Unintended Consequences of Medical Progress". Retrieved 18 November 2018. 
  34. ↑ "Hemophilia and Hemostasis: A Case-Based Approach to Management". Retrieved 18 November 2018. 
  35. ↑ "Hemophilia: The Royal Disease". Retrieved 18 November 2018. 
  36. ↑ "Haemophilia". Google Trends. Retrieved 25 February 2021. 
  37. ↑ "Hemophilia". books.google.com. Retrieved 25 February 2021. 
  38. ↑ "Hemophilia". wikipediaviews.org. Retrieved 24 February 2021. 
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