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Haemophilia

  • Haemophilia is an X-linked recessive bleeding disorder caused by partial or complete deficiency of blood clotting factors.
  • The two most common types are haemophilia A, which is caused by Factor VIII deficiency, and haemophilia B, which is caused by Factor IX deficiency. Haemophilia A occurs in 1 in 5,000 male births. The incidence of haemophilia B is 1 in 30,000 male births.
  • Haemophilia can result in prolonged bleeding and bruising after minor injury. Individuals with severe haemophilia may experience spontaneous bleeding in joints and muscles.
  • All patients with haemophilia should be managed at a specialist haemophilia centre.

Clinical features

The symptoms of haemophilia can be divided in to mild, moderate and severe.

Boys with severe haemophilia usually present early in infancy. Individuals with mild to moderate haemophilia may not present until adulthood.

  • Mild: excessive bleeding after surgery, dental extractions and accidents
  • Moderate: bleeding into joints and muscle after minor injury
  • Severe: spontaneous bleeding into joints and muscles

Bleeding into a joint can cause tightness and joint pain. The joint may be hot and swollen and difficult to move. Recurrent bleeding into joints without treatment can lead to long standing joint problems. Minor bumps to the head can lead to bleeding in the brain which may have serious complications.

Diagnosis

  • Haemophilia may be suspected in a male with a history of easy bruising or bleeding, or because of a family history of haemophilia. The diagnosis will usually be made in liaison with a haematologist.
  • Abnormalities can be detected on a routine blood clotting screen that may prompt further investigations. The diagnosis can be confirmed by measuring the levels of clotting factor in the blood. Individuals with haemophilia A will have reduced levels of clotting factor VIII. In haemophilia B the levels of clotting factor IX are reduced. The levels of clotting factor correspond to the severity of the disease.
  • As the genes responsibile for haemophilia are known, molecular genetic testing can be used to identify the alteration in a family if appropriate.

Genetic basis

  • Haemophilia is an X-linked recessive condition. This means that the gene alteration causing haemophilia is located on the X chromosome. Females have two copies of the X chromosome and males have one X chromosome and one Y chromosome.
  • If a male has an altered haemophilia gene on his X chromosome, then he will be affected with haemophilia. If a woman has an altered haemophilia gene on only one of her X chromosomes, then she is said to be a carrier. Some girls who are carriers of haemophilia may have slightly reduced factor levels, which predispose to minor bleeding.
  • If a female carrier of haemophilia has a boy, there is a 50% (1 in 2) chance that the boy will have haemophilia.
  • If a female carrier has a girl, there is a 50% (1 in 2) chance that the girl will be a carrier for haemophilia.
  • When men affected with haemophilia have children, all of their daughters will inherit the altered gene on the X chromosome and so will be carriers. Men do not pass on their X chromosome to their sons. Therefore, their sons will not be affected and will not be carriers.

Clinical management

  • Individuals with haemophilia should be managed at a specialist haemophilia centre.
  • The main aim of treatment is to try to prevent bleeding, pain and joint damage. This is achieved by replacing the missing clotting factor. Clotting factor concentrate needs to be given by intravenous injection.
  • Some individuals with moderate or severe haemophilia will be given prophylactic clotting factor on a regular basis to try to prevent bleeding. Treatment can also be given ‘on demand’, such as before surgical procedures or after injury has occurred.
  • In the UK all patients with haemophilia are entitled to receive artificial factor concentrates that are free from human plasma and therefore do not carry a risk of passing on blood-borne infections.

Genetic testing

  • Genetic testing can be used to confirm the diagnosis of haemophilia.
  • Carrier testing can be carried out for female relatives if the gene mutation is first identified in the affected individual. This is especially helpful, as measuring clotting factors is not always reliable in identifying female carriers.
  • Prenatal diagnosis can be considered for pregnancies at risk of severe haemophilia.
  • Males who are at risk of haemophilia can be tested at birth on cord blood to help guide further management.
  • A proportion of patients with haemophilia will produce antibodies (inhibitors) to the administered clotting factor, which can reduce their response to treatment. Information about the type of gene mutation can sometimes provide information about whether inhibitors are likely to be produced.

 

This information is intended for educational use and was current in August 2013. For clinical management, it is recommended that local guidelines and protocols are used.