Haemophilia A

Source: Wikipedia, the free encyclopedia.
This article is about the bleeding disorder with factor VIII deficiency. For the disorder with factor IX deficiency, see haemophilia B.

Haemophilia A
Other namesHemophilia A
Haematology
SymptomsProlonged bleeding from common injuries[1]
CausesFactor VIII deficiency[2]
Diagnostic methodBleeding time,[2] coagulation screen, genetic testing
PreventionHepatitis B vaccine should be considered[2]
TreatmentFactor VIII, factor VIII inhibitors, emicizumab

Haemophilia A (or hemophilia A) is a

de novo (spontaneous) mutations.[2][3][4]

The medical management of individuals with hemophilia A frequently entails the administration of

intravenous injection
. This intervention aims to address and preempt additional bleeding episodes in affected individuals.

Signs and symptoms

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

heelpricks. These signs often prompt blood tests that confirm the presence of haemophilia.[5] 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.[1] While superficial bleeding poses challenges, more critical sites of bleeding include:[6]

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

coagulation cascade, can be infused as a treatment for haemorrhage in individuals with haemophilia and antibodies against replacement factor VIII.[1][7]

Oral Manifestations

The oral manifestations are characterized by frequent bleeding of multiple sites, frequently seen as gingival and postextraction 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.[8]

Genetics

X linked recessive inheritance

Haemophilia A is inherited as an

heterozygous females due to X-inactivation, so it is recommended that levels of factor VIII and IX be measured in all known or potential carriers prior to surgery and in the event of clinically significant bleeding.[1][10]

About 5-10% of people with haemophilia A are affected because they make a dysfunctional version of the factor VIII protein, while the remainder are affected because they produce factor VIII in insufficient amounts (quantitative deficiency).[10] 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.[10]

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

known case of haemophilia is identified.[1][10] Approximately 30% of patients have no family history; their disease is presumably caused by new mutations.[11]

Diagnosis

X-Ray- haemoarthritis
Haemarthrosis on lateral view

The diagnosis of haemophilia A may be suspected as coagulation testing reveals an increased

tooth extraction, or surgery).[1]

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.[13]

Differential diagnosis

Two of the most common

von Willebrand Disease which is a deficiency in von Willebrand factor (needed for the proper functioning of Factor VIII[14]); haemophilia C is also considered.[3]

Treatment

Desmopressin
Recombinant factor VIII
for self-treatment.

In regards to the treatment of this genetic disorder, most individuals with severe haemophilia require regular supplementation with

intravenous antibiotics but sometimes the device must be removed,[17] 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.[18] Mild haemophiliacs often manage their condition with desmopressin, a drug which releases stored factor VIII from blood vessel walls.[19]

Dental considerations

The inferior alveolar nerve block 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.[20]

Gene therapy

In December 2017, it was reported that doctors had used a new form of gene therapy to treat haemophilia A.[21][22][23]

Monoclonal antibodies

Monoclonal antibody emicizumab has been approved by the FDA in 2017 for therapy of hemophilia A.[24]

Prognosis

Two Dutch studies have followed haemophilia patients for a number of years.

anti-retroviral drugs since these studies were done.[citation needed
]

Epidemiology

Haemophilia A occurs in approximately 1 in 5,000 males,[10] while the incidence of haemophilia B is 1 in 30,000 in the male population,[10] of these, 85% have haemophilia A and 15% have haemophilia B.[10]

See also

References

  1. ^
    PMID 20301578
    .update 2014
  2. ^ a b c d "Hemophilia A: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 24 June 2016.
  3. ^ a b "Haemophilia A (Factor VIII Deficiency) information | Patient". Patient. Retrieved 24 June 2016.
  4. ISBN 9789241547659
    .
  5. ISBN 9781118767429
    .
  6. ^ a b "How Is Hemophilia Treated? - NHLBI, NIH". www.nhlbi.nih.gov. Retrieved 2016-07-08.
  7. PMID 17124095
    .
  8. ^ 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.
  9. PMID 22754241
    .
  10. ^
    ISBN 978-1-4377-0755-7
    .
  11. PMID 11836440
    .
  12. ^ "OMIM Entry - # 306700 - HEMOPHILIA A; HEMA". omim.org. Retrieved 2016-07-08.
  13. ^ Hemophilia A at eMedicine
  14. ^ "Von Willebrand's Disease. About Von Willebrand's Disease | Patient". Patient. Retrieved 2016-07-08.
  15. ISBN 9781118439302
    .Google books no page
  16. PMID 19105504
    .
  17. ^ "Guidelines for the Prevention of Intravascular Catheter-Related Infections". www.cdc.gov. Retrieved 8 July 2016.
  18. S2CID 25748135
    .
  19. PMID 21839010
    .
  20. ^ 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).
  21. ^ "Groundbreaking gene therapy trial set to cure haemophilia A". Barts Health NHS Trust. 14 December 2017. Retrieved 14 December 2017.
  22. ^ "Haemophilia A trial results 'mind-blowing'". BBC. 14 December 2017. Retrieved 14 December 2017.
  23. PMID 29224506
    .
  24. ^ HEMLIBRA- emicizumab injection, solution drug label/data at DailyMed from U.S. National Library of Medicine, National Institutes of Health.
  25. S2CID 22008880
    .
  26. ^
    S2CID 13651790
    .

Further reading

External links

Scholia has a topic profile for Haemophilia A.
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