View source for Haemophilia A

{{About|the bleeding disorder with factor VIII deficiency|the disorder with factor IX deficiency|haemophilia B}}
{{Use British English|date=September 2023}}
{{Infobox medical condition
| name          = Haemophilia A
| synonyms      = Hemophilia A
| image         = Protein F8 PDB 1d7p.png
| caption       = Protein structure of coagulation factor VIII, of which its deficiency is the cause of haemophilia A.
| pronounce     =
| field         = [[Haematology]]
| symptoms      = Prolonged bleeding from common injuries<ref name=gen/>
| complications =
| onset         =
| duration      =
| types         =
| causes        = Factor VIII deficiency<ref name=nih/>
| risks         =
| diagnosis     = Bleeding time,<ref name=nih/> coagulation screen, genetic testing
| differential  =
| prevention    = Hepatitis B vaccine should be considered<ref name=nih/>
| treatment     = Factor VIII, factor VIII inhibitors, [[emicizumab]]
| medication    =
| prognosis     =
| frequency     =
| deaths        =
}}
'''Haemophilia A''' (or '''hemophilia A''') is a [[blood clotting disorder]] caused by a [[Genetic deficiencies|genetic deficiency]] in clotting [[factor VIII]], thereby resulting in significant susceptibility to bleeding, both internally and externally. This condition occurs almost exclusively in males born to carrier mothers due to [[X-linked recessive inheritance]]. Nevertheless, rare isolated cases do emerge from [[De novo mutations|de novo (spontaneous) mutations]].<ref name="nih">{{cite web|title=Hemophilia A: MedlinePlus Medical Encyclopedia|url=https://medlineplus.gov/ency/article/000538.htm|website=www.nlm.nih.gov|access-date=24 June 2016}}</ref><ref name="pat">{{cite web|title=Haemophilia A (Factor VIII Deficiency) information {{!}} Patient|url=http://patient.info/doctor/haemophilia-a-factor-viii-deficiency|website=Patient|access-date=24 June 2016}}</ref><ref name="WHO2008">{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | pages=259–60 }}</ref>

The medical management of individuals with hemophilia A frequently entails the administration of [[Factor VIII (medication)|factor VIII medication]] through slow [[intravenous injection]]. This intervention aims to address and preempt additional bleeding episodes in affected individuals.

==Signs and symptoms==
[[File:Gray299.png|thumb|Joint capsule]]
Haemophilia A's phenotype has a quite wide range of symptoms encompassing both internal and external bleeding episodes. Individuals with more severe haemophilia tend to experience more intense and frequent bleeding, whereas those with mild haemophilia typically exhibit milder symptoms unless subjected to surgical procedures or significant trauma. Those with moderate haemophilia may display variable symptoms, falling within the spectrum between severe and mild forms.

One common early indicator of haemophilia is prolonged bleeding from [[venepuncture]] or [[heelprick]]s. These signs often prompt blood tests that confirm the presence of haemophilia.<ref>{{Cite book|url=https://books.google.com/books?id=hcfvCQAAQBAJ|title=Neonatology at a Glance|last1=Lissauer|first1=Tom|last2=Fanaroff|first2=Avroy A.|last3=Miall|first3=Lawrence|last4=Fanaroff|first4=Jonathan|date=2015-06-10|publisher=John Wiley & Sons|page=135|isbn=978-1-118-76742-9|language=en}}</ref> In individuals, especially those with moderate or mild haemophilia, any form of trauma can trigger the first significant bleed. Haemophilia substantially elevates the risk of protracted bleeding from ordinary injuries, and in severe cases, bleeding can occur spontaneously without an apparent cause. Bleeding episodes can manifest anywhere in the body. Superficial bleeding resulting from abrasions or shallow lacerations may persist, with scabs easily breaking due to the deficiency of [[fibrin]], potentially leading to re-bleeding.<ref name="gen" /> While superficial bleeding poses challenges, more critical sites of bleeding include:<ref name="nih2" />
* [[Joint]]s
* [[Muscle]]s
* [[Digestive tract]]
* [[Brain]]

===Complications===
One therapeutic conundrum is the development of ''inhibitor'' antibodies against factor VIII due to frequent infusions. These develop as the body recognises the infused factor VIII as foreign, as the body does not produce its own ''copy''. In these individuals, activated [[factor VII]], a protein in the extrinsic pathway of the [[coagulation cascade]], can be infused as a treatment for haemorrhage in individuals with haemophilia and antibodies against replacement factor VIII.<ref name="gen">{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK1404/|title=Hemophilia A|last1=Konkle|first1=Barbara A.|last2=Josephson|first2=Neil C.|last3=Nakaya Fletcher|first3=Shelley|date=1993-01-01|publisher=University of Washington, Seattle|editor-last=Pagon|editor-first=Roberta A.|location=Seattle (WA)|pmid=20301578|editor-last2=Adam|editor-first2=Margaret P.|editor-last3=Ardinger|editor-first3=Holly H.|editor-last4=Wallace|editor-first4=Stephanie E.|editor-last5=Amemiya|editor-first5=Anne|editor-last6=Bean|editor-first6=Lora J.H.|editor-last7=Bird|editor-first7=Thomas D.|editor-last8=Fong|editor-first8=Chin-To|editor-last9=Mefford|editor-first9=Heather C.}}update 2014</ref><ref>{{Cite journal|last1=Ma|first1=Alice D.|last2=Carrizosa|first2=Daniel|date=2006-01-01|title=Acquired Factor VIII Inhibitors: Pathophysiology and Treatment|journal=ASH Education Program Book|language=en|volume=2006|issue=1|pages=432–437|doi=10.1182/asheducation-2006.1.432|issn=1520-4391|pmid=17124095|doi-access=free}}</ref>

=== Oral Manifestations ===
The oral manifestations are characterized by frequent bleeding of multiple sites, frequently seen as gingival and postextraction [[Bleeding|haemorrhages]]. The symptoms depend on the severity of haemophilia. In the case of severe haemophilia, patients may complain of multiple oral bleeding episodes throughout their life. Haemophilia patients are considered to be a special group of patients as routinely done procedures may be fatal in them. It was seen that almost 14% of all haemophilia patients and 30% of cases with a mild type of haemophilia have been diagnosed early following an episode of severe oral bleeding, of which the most common sites were the labial frenum and the tongue.<ref>''Sonu Acharya, Karishma Rathore, Upasana Mahapatra, Sashikant Sethi, Nikita Sahu (2018). "An unusual oral manifestation of hemophilia in a child". Journal of International Oral Health. Retrieved 2019-12-20.''</ref>

==Genetics==
[[Image: X recessive carrier mother.svg|thumb|200 px|X linked recessive inheritance]]
Haemophilia A is inherited as an [[X-linked]] [[recessive trait]]. It occurs in males and in [[homozygous]] females (which is only possible in the daughters of a haemophilic male and a carrier or haemophiliac female<ref>{{Cite journal|last1=Nair|first1=Preethi S.|last2=Shetty|first2=S.|last3=Ghosh|first3=Kanjaksha|date=2012-01-01|title=A homozygous female hemophilia A|journal=Indian Journal of Human Genetics|volume=18|issue=1|pages=134–136|doi=10.4103/0971-6866.96685|issn=0971-6866|pmc=3385172|pmid=22754241 |doi-access=free }}</ref>). However, mild haemophilia A is known to occur in [[heterozygous]] females due to [[X-inactivation]], so it is recommended that levels of factor VIII and [[Factor IX|IX]] be measured in all known or potential carriers prior to surgery and in the event of clinically significant bleeding.<ref name=gen/><ref name=Nelson>{{cite book|last=Kliegman|first=Robert|title=Nelson textbook of pediatrics.|year=2011|publisher=Saunders|location=Philadelphia|isbn=978-1-4377-0755-7|edition=19th |pages=1700–1}}</ref>

About 5-10% of people with haemophilia A are affected because they make a dysfunctional version of the [[Factor VIII|factor VIII protein]], while the remainder are affected because they produce factor VIII in insufficient amounts (quantitative deficiency).<ref name="Nelson" /> Of those who have severe deficiency (defined as <1% activity of factor VIII), 45-50% have the same mutation, an inversion within the factor VIII gene that results in total elimination of protein production.<ref name="Nelson" />

Since both forms of haemophilia can be caused by a variety of different mutations, initial diagnosis and classification is done by measurement of protein activity rather than by [[Genetic testing|genetic tests]], though genetic tests are recommended for testing of family members once a [[propositus|known case]] of haemophilia is identified.<ref name=gen/><ref name="Nelson" /> Approximately 30% of patients have no family history; their disease is presumably caused by new mutations.<ref>{{cite journal |last1=Bowen |first1=D J |title=Haemophilia A and haemophilia B: molecular insights |journal=Molecular Pathology |volume=55 |issue=1 |pages=1–18 |year=2002 |pmid=11836440 |pmc=1187139 |doi=10.1136/mp.55.1.1 }}</ref>

==Causes==
===Vaccine===
In 2022, it was reported that a man in his 80s developed Acquired [[Haemophilia A]] (AHA) two weeks after he got an injection of COVID-19 mRNA vaccine. Several tests demonstrated an isolated prolonged activated partial thromboplastin time (aPTT) not corrected immediately and low clotting factor VIII (FVIII) activity (6.7percent). Researchers hypothesized that the mRNA vaccination induced an autoimmune response, considering vaccines can activate nonspecific antibodies and stimulate autoantibody production.<ref> 
{{cite journal 
| title = Case of acquired haemophilia a in Southeast Asia following COVID-19 vaccine
| journal = British Medical Journal Case Report  
| volume = 12
| date = 2022 
| doi = 10.1136/bcr-2021-246922
| vauthors = ((Ai Vuen L, et. al.)) 
| issue = 3 
| article-number = e246922 
| pmid = 35264381 
| pmc = 8915366}}
</ref>

AHA patients are mostly aged over 65, but it was reported that a 45-year-old woman who had no medical condition suffered from AHA two weeks after receiving COVID-19 mRNA booster injection. Researchers observed a drop in FVIII activity (0.9 percent), prolonged aPPT (75.1 seconds), and confirmed FVIII inhibitor (12.8 BU/mL), and could find no indication that genetic factors were responsible for. Their study suggested that young adults could suffer from AHA after receiving COVID-19 mRNA shots.
<ref>
{{cite journal 
| title = Acute-type acquired hemophilia A after COVID-19 mRNA vaccine administration: A new disease entity?  
| journal = Journal of Antoimmunity  
| date = 2022
| doi = 10.1016/j.jaut.2022.102915
| vauthors = ((Hosoi, H. et. al.)) 
| volume = 133 
| article-number = 102915 
| pmid = 36155279 
| pmc = 9485432}}
</ref>

In 2024, Korean researchers reported that a 56-year-old man who had medical conditions such as diabetes and dyslipidemia was diagnosed with AHA 15 days after receiving his second dose of COVID-19 mRNA vaccine. It was Korea's first case of post-vaccination AHA concerning COVID-19 vaccine. They argued that monitoring individuals after COVID-19 vaccination was essential for detecting rare adverse effects.
<ref>
{{cite journal 
| title = Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review   
| journal = Medicine   
| date = 2024
| doi = 10.1097/MD.0000000000039166
| vauthors = ((Kim, HJ. et. al.)) 
| volume = 103 
| issue = 31 
| article-number = e39166 
| pmid = 39093750 
| pmc = 11296452}}
</ref>

==Diagnosis==
[[File:Medical X-Ray imaging JDH05 nevit.jpg|thumb|X-Ray- haemoarthritis]]
[[File:Medical X-Ray imaging JDG05 nevit.jpg|thumb|left|Haemarthrosis on lateral view]]

The diagnosis of haemophilia A may be suspected as coagulation testing reveals an increased [[partial thromboplastin time|partial thromboplastin time (PTT)]] in the context of a normal [[prothrombin time|prothrombin time (PT)]] and [[bleeding time]]. PTT tests are the first blood test done when haemophilia is indicated.<ref>{{Cite web|url=http://omim.org/entry/306700|title=OMIM Entry - # 306700 - HEMOPHILIA A; HEMA|website=omim.org|access-date=2016-07-08}}</ref> However, the diagnosis is made in the presence of very low levels of factor VIII. A [[Family history (medicine)|family history]] is frequently present, although not essential. Recently, [[genetic testing]] has been made available to determine an individual's risk of attaining or passing on haemophilia. Diagnosis of haemophilia A also includes a severity level, which can range from mild to severe based on the amount of active and functioning factor VIII detected in the blood. Factor VIII levels do not typically change throughout an individual's lifetime. Severe haemophilia A is the most common severity, occurring in the majority of affected people. Individuals with mild haemophilia often experience few or no bleeding episodes except in the case of serious [[Physical trauma|trauma]] (i.e. [[tooth extraction]], or [[surgery]]).<ref name=gen/>

===Severity===
There are numerous different mutations which can cause haemophilia A, due to differences in changes to the factor VIII gene (and the resulting protein). Individuals with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having ''severe haemophilia'', those with 1–5% active factor have ''moderate haemophilia'', and those with ''mild haemophilia'' have between 5–40% of normal levels of active clotting factor.<ref name=emed>{{EMedicine|article|210104|Hemophilia A}}</ref>

===Differential diagnosis===
Two of the most common [[differential diagnosis|differential diagnoses]] are [[haemophilia B]] which is a deficiency in [[Factor IX]] and [[von Willebrand Disease]] which is a deficiency in [[von Willebrand factor]] (needed for the proper functioning of Factor VIII<ref>{{Cite web|url=http://patient.info/doctor/von-willebrands-disease|title=Von Willebrand's Disease. About Von Willebrand's Disease {{!}} Patient|website=Patient|language=en-GB|access-date=2016-07-08}}</ref>); [[haemophilia C]] is also considered.<ref name=pat/>

==Treatment==
[[File:Desmopressin ball-and-stick.png|thumb|left|Desmopressin]]
[[File:Faktor-VIII.jpg|thumb|[[Recombinant factor VIII]] for self-treatment.]]
Most individuals with severe haemophilia require regular supplementation with [[intravenous]] [[Blood plasma|plasma]] concentrate [[Factor VIII (medication)|factor VIII]] or [[efanesoctocog alfa]], a [[von Willebrand factor]] (VWF) independent, recombinant DNA-derived Factor VIII (FVIII) concentrate shown to prevent bleeding in children and adults.<ref>{{Cite journal |last1=von Drygalski |first1=Annette |last2=Chowdary |first2=Pratima |last3=Kulkarni |first3=Roshni |last4=Susen |first4=Sophie |last5=Konkle |first5=Barbara A. |last6=Oldenburg |first6=Johannes |last7=Matino |first7=Davide |last8=Klamroth |first8=Robert |last9=Weyand |first9=Angela C. |last10=Jimenez-Yuste |first10=Victor |last11=Nogami |first11=Keiji |last12=Poloskey |first12=Stacey |last13=Winding |first13=Bent |last14=Willemze |first14=Annemieke |last15=Knobe |first15=Karin |date=2023-01-26 |title=Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A |url=http://www.nejm.org/doi/10.1056/NEJMoa2209226 |journal=New England Journal of Medicine |language=en |volume=388 |issue=4 |pages=310–318 |doi=10.1056/NEJMoa2209226 |pmid=36720133 |issn=0028-4793|hdl=2078.1/274138 |hdl-access=free }}</ref><ref>{{Cite journal |last1=Malec |first1=Lynn |last2=Peyvandi |first2=Flora |last3=Chan |first3=Anthony K.C. |last4=Königs |first4=Christoph |last5=Zulfikar |first5=Bulent |last6=Yuan |first6=Huixing |last7=Simpson |first7=Mindy |last8=Álvarez Román |first8=Maria Teresa |last9=Carcao |first9=Manuel |last10=Staber |first10=Janice M. |last11=Dunn |first11=Amy L. |last12=Chou |first12=Sheng-Chieh |last13=d'Oiron |first13=Roseline |last14=Albisetti |first14=Manuela |last15=Demissie |first15=Marek |date=2024-07-18 |title=Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A |url=http://www.nejm.org/doi/10.1056/NEJMoa2312611 |journal=New England Journal of Medicine |language=en |volume=391 |issue=3 |pages=235–246 |doi=10.1056/NEJMoa2312611 |pmid=39018533 |issn=0028-4793|url-access=subscription }}</ref> Treatment dosing and frequency of plasma concentrate Factor VIII may be variable and individually determined;<ref name="nih2">{{Cite web|url=https://www.nhlbi.nih.gov/health/bleeding-disorders/treatment|title=How Is Hemophilia Treated? - NHLBI, NIH|website=www.nhlbi.nih.gov|access-date=2016-07-08}}</ref> dosing of efanesoctocog alfa shown effective is an IV injection of once-weekly  50 IU per kilogram of body weight.

In children, an easily accessible intravenous port<ref>{{Cite book|url=https://books.google.com/books?id=JeCD7cUVeTEC|title=Hemophilia and Hemostasis: A Case-Based Approach to Management|last1=Ma|first1=Alice D.|last2=Roberts|first2=Harold R.|last3=Escobar|first3=Miguel A.|date=2012-10-03|publisher=John Wiley & Sons|isbn=978-1-118-43930-2|language=en}}Google books no page</ref> may have to be inserted to minimise frequent traumatic intravenous [[cannulation]]. These devices have made [[prophylaxis]] in haemophilia much easier for families because the problems of finding a vein for [[infusion]] several times a week are eliminated. However, there are risks involved with their use, the most worrisome being that of infection, studies differ but some show an infection rate that is high.<ref>{{Cite journal|last1=Santagostino|first1=Elena|last2=Mancuso|first2=Maria Elisa|date=2008-09-01|title=Barriers to primary prophylaxis in haemophilic children: the issue of the venous access|journal=Blood Transfusion|volume=6|issue=Suppl 2|pages=s12–s16|doi=10.2450/2008.0031-08|issn=1723-2007|pmc=2652218|pmid=19105504}}</ref> These infections can usually be treated with [[intravenous]] antibiotics but sometimes the device must be removed,<ref>{{cite web|title=Guidelines for the Prevention of Intravascular Catheter-Related Infections|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5110a1.htm|website=www.cdc.gov|access-date=8 July 2016}}</ref> also, there are other studies that show a risk of clots forming at the tip of the catheter, rendering it useless. Some individuals with severe haemophilia, and most with moderate and mild haemophilia, treat only as needed without a regular prophylactic schedule.<ref>{{Cite journal|last=Ljung|first=Rolf|date=2007-09-01|title=The risk associated with indwelling catheters in children with haemophilia|journal=British Journal of Haematology|language=en|volume=138|issue=5|pages=580–586|doi=10.1111/j.1365-2141.2007.06703.x|issn=1365-2141|pmid=17686052|s2cid=25748135|doi-access=free}}</ref> Mild haemophiliacs often manage their condition with [[desmopressin]], a drug which releases stored factor VIII from blood vessel walls.<ref>{{Cite journal|last1=Franchini|first1=Massimo|last2=Lippi|first2=Giuseppe|date=2011-10-01|title=The use of desmopressin in acquired haemophilia A: a systematic review|journal=Blood Transfusion|volume=9|issue=4|pages=377–382|doi=10.2450/2011.0113-10|issn=1723-2007|pmc=3200405|pmid=21839010}}</ref>

[[Fitusiran]] (Qfitlia) was approved for medical use in the United States in March 2025.<ref name="FDA PR 20230328">{{cite web | title=FDA Approves Novel Treatment for Hemophilia A or B, with or without Factor Inhibitors | website=U.S. Food and Drug Administration | date=28 March 2025 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-novel-treatment-hemophilia-or-b-or-without-factor-inhibitors | access-date=29 March 2025}}</ref><ref>{{cite press release | title=Qfitlia approved as the first therapy in the US to treat hemophilia A or B with or without inhibitors | website=Sanofi | date=28 March 2025 | url=https://www.news.sanofi.us/2025-03-28-Qfitlia-approved-as-the-first-therapy-in-the-US-to-treat-hemophilia-A-or-B-with-or-without-inhibitors | access-date=29 March 2025}}</ref>

=== Dental considerations ===
If numbing is necessary for dental procedures, the nerve block (typically to the inferior alveolar nerve) should only be given after raising clotting factor levels by appropriate replacement therapy, as there is a risk of bleeding into the muscles along with potential airway compromise due to a haematoma in the retromolar or pterygoid space. The intraligamental technique or interosseous technique should be considered instead of the mandibular block. Articaine has been used as a buccal infiltration to anaesthetize the lower molar teeth. A lingual infiltration also requires appropriate factor replacement since the injection is into an area with a rich plexus of blood vessels and the needle is not adjacent to bone.<ref>''Andrew Brewer, Maria Elvira Correa (May 2006). "Guildelines for Dental Treatment of Patients with Inherited Bleeding Disorders" (PDF). Treatment of Hemophilia. '''40''': 9 – via World Federation of Hemophilia (WFH).''</ref>

===Gene therapy===
In December 2017, it was reported that doctors had used a new form of [[gene therapy]] to treat haemophilia A.<ref>{{cite web|url=https://www.bartshealth.nhs.uk/news/groundbreaking-gene-therapy-trial-set-to-cure-haemophilia-a-2529|title=Groundbreaking gene therapy trial set to cure haemophilia A|date=14 December 2017|work=Barts Health NHS Trust|access-date=14 December 2017}}</ref><ref>{{cite web|url=https://www.bbc.com/news/health-42337396|title=Haemophilia A trial results 'mind-blowing'|date=14 December 2017|work=BBC|access-date=14 December 2017}}</ref><ref>{{cite journal|title=AAV5–Factor VIII Gene Transfer in Severe Hemophilia A|date=16 December 2017|journal=New England Journal of Medicine|volume=377|issue=26|pages=2519–2530|doi=10.1056/NEJMoa1708483|pmid=29224506|last1 = Rangarajan|first1 = Savita|last2=Walsh|first2=Liron|last3=Lester|first3=Will|last4=Perry|first4=David|last5=Madan|first5=Bella|last6=Laffan|first6=Michael|last7=Yu|first7=Hua|last8=Vettermann|first8=Christian|last9=Pierce|first9=Glenn F.|last10=Wong|first10=Wing Y.|last11=Pasi|first11=K. John|hdl=10044/1/57163|url=http://qmro.qmul.ac.uk/xmlui/handle/123456789/31880|doi-access=free|hdl-access=free}}</ref> Current treatment efforts utilize adeno-associated virus (AAV) vectors, however recent studies have found lentiviral vectors (LV) as being a more effective alternative.<ref>{{Cite journal |last1=Marchesini |first1=Emanuela |last2=Morfini |first2=Massimo |last3=Valentino |first3=Leonard |date=2021-06-15 |title=Recent Advances in the Treatment of Hemophilia: A Review |journal=Biologics: Targets and Therapy |language=English |volume=15 |pages=221–235 |doi=10.2147/BTT.S252580|doi-access=free |pmid=34163136 |pmc=8214539 }}</ref><ref>{{Cite journal |last1=Milani |first1=Michela |last2=Canepari |first2=Cesare |last3=Assanelli |first3=Simone |last4=Merlin |first4=Simone |last5=Borroni |first5=Ester |last6=Starinieri |first6=Francesco |last7=Biffi |first7=Mauro |last8=Russo |first8=Fabio |last9=Fabiano |first9=Anna |last10=Zambroni |first10=Desirèe |last11=Annoni |first11=Andrea |last12=Naldini |first12=Luigi |last13=Follenzi |first13=Antonia |last14=Cantore |first14=Alessio |date=2024-04-29 |title=GP64-pseudotyped lentiviral vectors target liver endothelial cells and correct hemophilia A mice |journal=EMBO Molecular Medicine |language=en |volume=16 |issue=6 |pages=1427–1450 |doi=10.1038/s44321-024-00072-8 |issn=1757-4684 |pmc=11178766 |pmid=38684862}}</ref>

=== Monoclonal antibodies ===
The [[Monoclonal antibody]] [[emicizumab]] (Hemlibra) was approved by the FDA in 2017.<ref>{{cite web | title=Hemlibra (emicizumab-kxwh) Injection | website=accessdata.fda.gov | date=29 December 2017 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761083Orig1s000TOC.cfm | access-date=29 March 2025}}</ref>

A study published in July 2024, demonstrated that [[efanesoctocog alfa]], a bioengineered human [[factor VIII]] recombinant protein, prophylaxis for children with severe hemophilia A could have therapeutic benefit leading to effective bleeding prevention.<ref>{{Cite journal |last1=Malec |first1=Lynn |last2=Peyvandi |first2=Flora |last3=Chan |first3=Anthony K.C. |last4=Königs |first4=Christoph |last5=Zulfikar |first5=Bulent |last6=Yuan |first6=Huixing |last7=Simpson |first7=Mindy |last8=Álvarez Román |first8=Maria Teresa |last9=Carcao |first9=Manuel |last10=Staber |first10=Janice M. |last11=Dunn |first11=Amy L. |last12=Chou |first12=Sheng-Chieh |last13=d'Oiron |first13=Roseline |last14=Albisetti |first14=Manuela |last15=Demissie |first15=Marek |date=2024-07-18 |title=Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A |url=http://www.nejm.org/doi/10.1056/NEJMoa2312611 |journal=New England Journal of Medicine |language=en |volume=391 |issue=3 |pages=235–246 |doi=10.1056/NEJMoa2312611 |pmid=39018533 |issn=0028-4793|url-access=subscription }}</ref><ref>{{Cite journal |last=Chowdary |first=Pratima |date=2024-07-18 |editor-last=Phimister |editor-first=Elizabeth G. |title=Bioengineered Factor VIII — More Innovation for Hemophilia A |url=http://www.nejm.org/doi/10.1056/NEJMe2313795 |journal=New England Journal of Medicine |volume=391 |issue=3 |pages=277–282 |doi=10.1056/NEJMe2313795 |pmid=39018538 |issn=0028-4793|url-access=subscription }}</ref>

== Prognosis ==
Two Dutch studies have followed haemophilia patients for a number of years.<ref>{{Cite journal|last=Triemstra|first=Mattanja|date=1995-12-01|title=Mortality in Patients with Hemophilia: Changes in a Dutch Population from 1986 to 1992 and 1973 to 1986|journal=Annals of Internal Medicine|volume=123|issue=11|pages=823–7|doi=10.7326/0003-4819-123-11-199512010-00002|pmid=7486463|s2cid=22008880|issn=0003-4819}}</ref><ref name=":0">{{Cite journal|last1=Plug|first1=I.|last2=Van Der Bom|first2=J. G.|last3=Peters|first3=M.|last4=Mauser-Bunschoten|first4=E. P.|last5=De Goede-Bolder|first5=A.|last6=Heijnen|first6=L.|last7=Smit|first7=C.|last8=Willemse|first8=J.|last9=Rosendaal|first9=F. R.|date=2006-03-01|title=Mortality and causes of death in patients with hemophilia, 1992–2001: a prospective cohort study1|journal=Journal of Thrombosis and Haemostasis|language=en|volume=4|issue=3|pages=510–516|doi=10.1111/j.1538-7836.2006.01808.x|pmid=16460432|issn=1538-7836|hdl=1887/5021|s2cid=13651790|hdl-access=free}}</ref> Both studies found that [[Viral disease|viral infections]] were common in haemophiliacs due to the frequent [[blood transfusion]]s which put them at risk of acquiring [[Blood-borne disease|blood borne infections]], such as [[HIV]], [[hepatitis B]] and [[hepatitis C]]. In the latest study which followed patients from 1992 to 2001, the male life expectancy was 59 years. If cases with known viral infections were excluded, the life expectancy was 72, close to that of the general population. 26% of the cases died from AIDS and 22% from hepatitis C.<ref name=":0" /> However, these statistics for prognosis are unreliable as there has been marked improvement of [[infection control]] and efficacy of [[anti-retroviral drugs]] since these studies were done.{{citation needed|date=August 2018}}

==Epidemiology==
Haemophilia A occurs in approximately 1 in 5,000 males,<ref name="Nelson" /> while the incidence of haemophilia B is 1 in 30,000 in the male population,<ref name="Nelson" /> of these, 85% have haemophilia A and 15% have [[haemophilia B]].<ref name="Nelson" />

==See also==
{{columns-list|colwidth=30em|
* [[Haemophilia]]
* [[Contaminated haemophilia blood products]]
* [[Ryan White]]
* [[Haemophilia B]]
* [[Haemophilia C]]
}}

==References==
{{Reflist}}

==Further reading==
* {{Cite journal|last1=Casana|first1=P.|last2=Cabrera|first2=N.|last3=Cid|first3=A. R.|last4=Haya|first4=S.|last5=Beneyto|first5=M.|last6=Espinos|first6=C.|last7=Cortina|first7=V.|last8=Dasi|first8=M. A.|last9=Aznar|first9=J. A.|date=2008-07-01|title=Severe and moderate hemophilia A: identification of 38 new genetic alterations|journal=Haematologica|language=en|volume=93|issue=7|pages=1091–1094|doi=10.3324/haematol.12344|issn=0390-6078|pmid=18403393|doi-access=free|hdl=10251/201248|hdl-access=free}}
* {{cite book|last1=Roberts|first1=Harold R.|title=Haemophilia and Haemostasis: A Case-based Approach to Management|publisher=John Wiley & Sons|isbn=978-0-470-76643-9|url=https://books.google.com/books?id=Qz2XlnVC1f8C&q=Haemophilia+A++diagnosis&pg=PA37|access-date=8 July 2016|language=en|date=2008-04-15}}
* {{cite journal|last1=Collins|first1=Peter|last2=Baudo|first2=Francesco|last3=Huth-Kühne|first3=Angela|last4=Ingerslev|first4=Jørgen|last5=Kessler|first5=Craig M|last6=Castellano|first6=Maria E Mingot|last7=Shima|first7=Midori|last8=St-Louis|first8=Jean|last9=Lévesque|first9=Hervé|title=Consensus recommendations for the diagnosis and treatment of acquired hemophilia A|journal=BMC Research Notes|date=7 June 2010|volume=3|article-number=161|doi=10.1186/1756-0500-3-161|issn=1756-0500|pmc=2896368|pmid=20529258 |doi-access=free }}
* {{cite journal|last1=Coppola|first1=Antonio|last2=Windyga|first2=Jerzy|last3=Tufano|first3=Antonella|last4=Yeung|first4=Cindy|last5=Di Minno|first5=Matteo Nicola Dario|title=Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery|journal=Cochrane Database of Systematic Reviews|issue=2|article-number=CD009961|date=9 February 2015|doi=10.1002/14651858.cd009961.pub2|pmid=25922858|language=en|doi-access=|pmc=11245682}}
* {{cite journal|last1=Kellogg|first1=TF|title=Steroid balance and tissue cholesterol accumulation in germfree and conventional rats fed diets containing saturated and polyunsaturated fats.|journal=Journal of Lipid Research|date=November 1974|volume=15|issue=6|pages=574–9|pmid=4430880|issn=0253-0716}}
* {{cite journal|last1=Armstrong|first1=Elina|last2=Hillarp|first2=Andreas|title=Assay discrepancy in mild haemophilia A|journal=European Journal of Haematology. Supplementum|volume=76|pages=48–50|doi=10.1111/ejh.12374|issn=0902-4506|pmid=24957107|year=2014|s2cid=205100329|doi-access=}}

== External links ==
{{Medical resources
|   DiseasesDB     = 5555
|   ICD11          = {{ICD11|3B10}}
|   ICD10          = {{ICD10|D|66||d|65}}
|   ICD9           = {{ICD9|286.0}}
|   ICDO           =
|   OMIM           = 306700
|   MedlinePlus    = 000538
|   eMedicineSubj  = emerg
|   eMedicineTopic = 239<!-- |  param?         = D006467 -->
}}
{{Commons}}

{{Scholia|topic}}
{{Diseases of megakaryocytes}}
{{X-linked disorders}}

[[Category:Haemophilia]]
[[Category:Defects of enzyme cofactors]]
[[Category:X-linked recessive disorders]]
[[Category:Coagulopathies]]