Skip to main content
Public beta This website is in public beta – please give your feedback.
Conditions

Haemophilia A

Haemophilia A is an inherited bleeding disorder associated with reduced levels of the blood clotting protein factor VIII.

Overview

Haemophilia A (also called factor VIII deficiency) is an X-linked inherited blood clotting disorder. Patients have reduced levels of a blood clotting protein called factor VIII. The exact symptoms depend upon severity of the condition and broadly reflect the level of factor VIII for that patient. Symptoms can include prolonged bleeding following injury or a procedure, with severely affected patients having spontaneous bleeding. All children with haemophilia should be referred to a haemophilia comprehensive care centre.

Clinical features

Haemophilia A is subdivided by severity into mild, moderate and severe. In general, the greater the severity of haemophilia the earlier the condition presents. Some children are referred following investigation of increased bruising or following prolonged bleeding after a procedure.

In around two-thirds of cases there will be a known family history. At-risk children can be diagnosed shortly after birth following cord blood sampling.

Severe haemophilia A

Patients with a factor VIII activity of <0.01IU/mL or <1IU/dL (<1%) are at risk of spontaneous bleeding. Neonates and infants can rarely present with intracranial bleeding in the perinatal period with a median age of presentation of six months. Children can also develop spontaneous joint or muscle bleeds. All children with severe haemophilia need regular early prophylaxis to prevent serious bleeding and to preserve joint health.

Moderate haemophilia A

Patients with a factor VIII activity of between 0.01–0.05IU/mL or 1–5IU/dL (1%–5%) generally present with bleeding in association with trauma. Spontaneous bleeding can occur, but is much less common that in severe forms. Children with moderate haemophilia A should be considered for regular prophylaxis to maintain joint health

Mild haemophilia A

For patients with a factor VIII activity of >0.05IU/mL or >5IU/dL (>5%), bleeding symptoms can vary widely: from a mild increase in bruising compared to their peers, to joint bleeds which are usually precipitated by trauma. Some patients will have only mild increase in bruising compared to their peers. Patients are treated “on demand” and regular treatment is generally not required.

Genomics

Haemophilia A is caused by pathogenic variants in the F8 gene which is found on the long arm of the X-chromosome (Xq28). The gene encodes the coagulation factor VIII protein. In around one-third of cases the variant is de novo in the patient and there is no family history.

Inversions in the F8 gene, which generally cause an absence of detectable factor VIII protein, are identified in approximately 45% of individuals with severe haemophilia A. In other patients, smaller deletions, insertions and point mutations are seen and the functional impact of these depends upon protein domain affected. More than 100 different point mutations have been described.

Establishing the causative variant in haemophilia A is important as some variants are known to be associated with particular severity of disease. Additionally, some variants are associated with increased risk of developing inhibitory antibodies to factor VIII, and this has important implications for treatment.

Around 50% of carrier females (see below for more information about inheritance) have clinically significant bleeding symptoms, with around 30% of carriers having factor VIII levels of <40IU/dL. Rarely, carrier females can be severely affected as a result of the the working gene being silenced; for example due to Turner syndrome (XO), compound heterozygosity or complete X-chromosome inactivation.

Female siblings of affected boys (or indeed any known or suspected carrier) should have their factor VIII levels tested during childhood to determine baseline levels. They may also need follow-up depending on their results and symptoms. Predictive genetic testing in asymptomatic relatives is considered once individuals are able to consent for themselves, which is generally in their mid-teens.

Reproductive options are available to carriers at risk of having affected children. This includes testing in early pregnancy and pre-implantation genetic testing (PGT), which is an IVF-based technique in which embryos without a given genetic condition are transferred. Women who may be carriers should be offered the opportunity to discuss genetic testing before having children so that they can consider these options. In addition, carrier status and factor VIII levels should be obtained to ensure the correct management of the woman herself during pregnancy and delivery, and to manage risks for a potentially affected infant. If carrier testing has not been carried out before pregnancy then it should be done as early as possible during the pregnancy.

Diagnosis

This condition may be identified before any symptoms appear, for example through the Generation Study. Therefore, management of these individuals may differ from those presenting symptomatically. Confirmation of the diagnosis will require referral to local genetic and haematology services. Please refer to the local pathway for your region for this condition.

This condition may also be identified before any symptoms appear in the newborn period, such as via cord blood testing in infants known to be at risk due to their family history.

Haemophilia may be suspected due to clinical symptoms and a prolonged APTT (activated partial thromboplastin time), which is a screening test of coagulation. Diagnosis is via a factor VIII activity assay. The level of factor VIII generally reflects the bleeding risk.

Confirmation of the diagnosis will require referral to a haemophilia comprehensive care centre. Any patient with a potential diagnosis of haemophilia, particularly if severe, should be urgently referred via same day telephone discussion with the haemophilia centre. Please refer to the local pathway for your region for this condition.

Genetic testing can be targeted specifically to factor VIII, or a broader testing of factor VIII alongside other causes of bleeding and platelet disorders can be undertaken.

Inheritance and genomic counselling

Haemophilia A is an X-linked recessive condition.

  • X-linked recessive conditions are usually only present in males.
  • Males with X-linked conditions cannot pass the variant on to their sons, but they always pass their affected X chromosome to their daughters. If the condition is recessive, their daughters will be carriers for the condition.
  • Female carriers of X-linked recessive conditions have a second, working copy of the gene and are therefore usually unaffected, or affected only mildly.
  • Sons of female carriers of X-linked recessive conditions have a 1 in 2 (50%) chance of being affected by the condition, and their daughters have a 1 in 2 (50%) chance of being carriers.

If a patient is diagnosed, a family history should be taken and careful consideration given to the possibility that other family members could be affected, especially male siblings. Screening and testing for the familial variant should be offered as appropriate.

Ideally the carrier status of a woman at risk of being a carrier of haemophilia A should be determined prior to pregnancy, or as early on in pregnancy as possible.

Education and counselling for female carriers of haemophilia A is generally provided by the adult haemophilia services and any pregnancy managed in conjunction with the local obstetric team including discussion around place and mode of delivery and management of the neonate.

Prenatal diagnosis is possible in pregnancies at risk of haemophilia A, including non-invasive prenatal diagnosis (NIPD) to determine the sex of the fetus. NIPD fetal sexing can be carried out from about 7–8 weeks gestation, followed by the option of invasive testing including chorionic villous sampling (CVS) and amniocentesis, if the pregnancy is male.

Reproductive options are available for those at risk of having a child with haemophilia A. Options typically include IVF with preimplantation genetic testing for monogenic disorders (PGT-M), or testing in early pregnancy. Genetic counselling is recommended, ideally prior to conception, to discuss the options. In the context of early pregnancy, urgent referral for genetic counselling should be considered.

Management

Individuals with haemophilia A (affected males and carrier females) should be under the care of a haemophilia comprehensive care centre. Management is multidisciplinary and includes education around the condition, how to recognise and treat bleeding and regular physiotherapy. All children with severe haemophilia A will need to start prophylaxis. Prophylaxis is now offered to all children with moderate haemophilia. Options for prophylaxis include factor VIII based treatment (both standard half life and extended half life therapies) and also non-factor therapy (in UK currently for severe patients only).

Management of babies and children with the condition should be delivered by a haemophilia consultant, and for severe and moderate patients this will be at a haemophilia comprehensive care centre. Some mild patients may be registered at a haemophilia centre closer to home.

Counselling of a pregnant woman who is known to be, or at risk of being a carrier of haemophilia A is via adult haemophilia services and in conjunction with obstetrics.

Controversy remains surrounding indications for caesarean section rather than vaginal delivery if the pregnancy is male and proven or at risk of having haemophilia A. The risks of each method of delivery should be discussed with the pregnant woman to enable her to make an informed decision.

This condition may be identified before any symptoms appear, for example through the Generation Study. Therefore, management of these individuals may differ from those presenting symptomatically.

For further information about management please see the resources section.

Resources

For clinicians

References:

For patients

↑ Back to top
  • Last reviewed: 22/05/2026
  • Next review due: 22/05/2029
  • Authors: Lisa Hughes, Dr Anne Kelly, Yvonne Muwalo
  • Reviewers: Dr Anne Kelly, Dr Joanna Kennedy, Dr Alice Taylor, Jessica Woods