What are the effects and signs?
Haemophilia A and B
Children with haemophilia experience bleeding into the tissues of the body after a trivial injury or sometimes spontaneously. The bleeding may occur into joints, muscles, abdomen or the brain. The probability of bleeding and the risk of a severe bleed depend on how little normal clotting factor is produced. This is measured in international units per decilitre (iu/dl) with a normal range of 50-150 iu/dl (for children under 6 months old the normal ranges for Factor IX are lower). A person with haemophilia will produce less than this, the lower the value the higher the risk of bleeding. This can be used to categorise haemophilia into severe (<1iu/dl), moderate (1-5iu/dl) and mild (5-50iu/dl). Sometimes these values are expressed as a percentage of normal clotting factor so severe (<1iu/dl) may be expressed as less than 1% of normal clotting factor levels. Moderate haemophilia (1-5iu/dl) may be expressed as 1-5% of normal clotting factor levels. Mild haemophilia (5-50iu/dl) may be expressed as 5-25% of normal clotting factor levels. These categories refer to the amount of clotting factor produced and not the disability experienced. Disability will depend on how many severe bleeds there have been and whether these have resulted in long term damage.
Inhibitors
Inhibitors can sometimes be a troublesome complication in the treatment of haemophilia. They can range from being mild to severe. They occur when the immune systems of people being treated with blood clotting agents, such as nonacog alfan, start to regard the clotting agents as foreign objects.
The immune system will start to create antibodies to block the effects of the clotting agent. These antibodies are known as inhibitors. These inhibitors can make the medication that is used to treat haemophilia less effective, which means that it is more difficult to prevent and control the symptoms of bleeding.
An estimated 15-25% of people who receive treatment for haemophilia A develop inhibitors.
An estimated 1.5-3% of people who receive treatment for haemophilia B develop inhibitors.
Severe haemophilia means less than <1iu/dl of Factor VIII or Factor IX are found in the blood (less than 1% of normal clotting factor levels)
Boys with severe haemophilia experience serious bleeding episodes. The condition may present soon after birth for example with bleeding into the scalp of a newly delivered infant. Bleeding occurs after mild or trivial injury and sometimes spontaneously. Bleeding into joints and muscles is a common problem. The joints most commonly affected are the knee, elbow, ankles, shoulder, wrist and hip. Repeated bleeds into joints leads to long term damage in the form of severe arthritis and sometimes deformity and reduced range of joint movement. The joint damage rather than the bleeding episodes themselves are the cause of disability. Since the late 1990s prophylactic (preventative) treatment has been introduced to prevent such bleeds and boys with severe haemophilia born since then may escape serious joint damage. Anyone born prior to the 1990s (or outside the UK in a place where treatment is not available) with severe haemophilia is likely to have some joint damage. Many will have multiple affected joints and enduring disability related to this, despite now using prophylactic treatment to prevent further bleeds and joint damage.
Bleeding into tissue causes haematoma formation, a haematoma is a collection of blood. Haematomas can damage surrounding tissue through pressure effects; the brain is especially at risk as it is housed in a non-expandable space inside the skull. Haemorrhage into the brain may be life threatening and can cause long term disability, an intracranial bleed may cause the following enduring effects:
- cerebral palsy
- neurological deficits
- epilepsy
Haematomas elsewhere in the body can cause muscle damage or peripheral nerve damage. Bleeding into large spaces such as the abdomen can result in extensive blood loss from the circulation, such bleeds are life threatening.
Frequency of bleeding episodes varies between individuals. Without prophylactic treatment some boys experience bleeds several times a week in others they may occur only a few times a year.
Moderate haemophilia - Factor VIII or Factor IX 1-5iu/dl (1-5% of normal clotting factor levels)
Bleeding tends to occur after trauma or injury, which can be minor. Spontaneous bleeding does not usually occur. If not treated episodes of bleeding may cause joint or neurological damage as described above in severe haemophilia.
Mild haemophilia – Factor VIII or Factor IX 5-50iu/dl (5-25% of normal clotting factor levels)
Abnormal bleeding tends only to reveal itself after significant injury, surgery or tooth extraction. Treatment of clotting factor deficiency is only required at these times. Life is normal otherwise and joint related or neurological disability from bleeds does not occur.
Female haemophilia carriers
Abnormal bleeding may occur after surgery or tooth extraction as some carriers will have low levels of clotting factor. The levels are very variable and may be under 20iu/dl. The carrier state is unlikely to be recognised unless there is a bleeding event that prompts investigation or a family history leading to genetic testing. Life is normal and there is no associated disability.
