Haemophilia B

Haemophilia B (also known as Factor IX deficiency) is a type of clotting disorder, much rarer than Haemophilia A (Factor VIII deficiency). A specific protein is missing from the blood so that injured blood vessels cannot heal in the usual way. This information sheet from Great Ormond Street Hospital (GOSH) explains the causes, symptoms and treatment of Haemophilia B and where to get help.

A clotting (or coagulation) disorder is a medical condition where a specific protein is missing from the blood.

Blood is made up of different types of cells (red blood cells, white blood cells and platelets) all suspended in a straw-coloured liquid called plasma. Platelets are the cells responsible for making blood clot. When a blood vessel is injured, platelets clump together to block the injury site. They also start off a complicated chemical reaction to form a mesh made of a substance called fibrin. This complicated chemical reaction always follows a strict pattern – with each clotting protein (known as a coagulation factor) turned on in order. When all of the factors are turned on, the blood forms a clot which stops the injury site bleeding any further.

There are a number of coagulation factors circulating in the blood, lying in wait to be turned on when an injury occurs. If any one of the factors is missing from the body, the complicated chemical reaction described above will not happen as it should. This can lead to blood loss, which can be severe and life-threatening. Each coagulation factor is given a number from I to XIII – they are always written as Roman numerals – and the effects of the missing factor will vary.

Haemophilia B is a type of clotting disorder. The specific coagulation factor that is missing or reduced in people with Haemophilia B is Factor IX. The severity of symptoms ranges from mild to severe depending on the amount of Factor IX present in the blood and its activity.

Haemophilia B is caused by a variant/mutation

(change) on the Factor IX gene on the

X-chromosome (specifically at location Xq27.1-q27-2), which means that only boys are affected and the mother is a carrier of the disease. In most cases, this mutation is passed on from parent to child. However in around 1/3 of cases it will be a new variant in the child which occurs sporadically (out of the blue), with no family history of bleeding disorders.

Human beings have about 30,000 to 40,000 different genes, each of which has a function in making an individual person. The genes are arranged in pairs (one of the pair from each parent) on 23 chromosomes – inevitably some of these genes are faulty.

The chromosome that determines the gender of the child will either contain ‘XX’ (female) or ‘XY’ (male).

Haemophilia B is inherited as an X-linked condition. As females have two ‘X’ chromosomes, the fault can be completely or partially overcome by the other healthy ‘X’ in the pair but in males, who only have one ‘X’, there is not another ‘X’ to provide a functioning gene. Unless there have been other affected boys in the family there may be no way of knowing whether the mother is a carrier, as most carriers remain healthy.

Each pregnancy carries a:

• 25 per cent chance of the child being an unaffected non-carrier girl
• 25 per cent chance of the child being a carrier girl (who may have mildly reduced FIX levels)
• 25 per cent chance of the child being an unaffected boy
• 25 per cent chance of the child being an affected boy.

If a man with Haemophilia B has children, all of his daughters will be carriers but his sons will not have the condition nor carry the gene mutation to pass it on to his children. Carrier females may have mildly low levels and mild bleeding problems, such as heavy periods, but these are not usually severe enough to need regular treatment. We do not usually test the genetics of a female patient until they are old enough to decide for themselves which is generally in their teens.

The age at which symptoms appear varies, depending on the amount of Factor IX in the blood and how well it is working. Children with little or no Factor IX may start to show symptoms soon after birth, whereas those with some functioning Factor IX may not show symptoms until later, often following surgery or injury.

Bleeding is the best known symptom of Haemophilia B – people with the condition may bleed more severely following injury or for a longer time. This is because the level of

Factor IX in the blood is too low to complete the clotting process as described earlier. Bleeding may occur inside the body as well as from the skin – this can include bleeds inside the joints. It can follow an injury or sometimes no trigger occurs – this is called a ‘spontaneous bleed’. Over time, each bleed can damage the joint making it swollen and harder to bend. Bruising is also common in people with Haemophilia B. Other areas of the body may develop bleeds, such as the digestive or urinary systems, where blood may be visible in the faeces or urine. Nose bleeds can also happen spontaneously.

Haemophilia B can be diagnosed before birth (prenatally) if there is a family history of haemophilia. There are several options for this including chorionic villus sampling (CVS) early in pregnancy or amniocentesis around 15- 20 weeks.. An alternative is free-foetal DNA testing – this does not diagnose haemophilia but it can identify the sex of the baby in the womb, which is particularly helpful in X-linked disorders that mainly affect males.

After birth, Haemophilia B can be diagnosed using a sample of blood for testing in the laboratory. A test to measure how long a sample takes to clot may suggest a clotting disorder, which would then be investigated further. Doctors will try to identify the gene mutation as well, as this can be helpful in planning future brothers and sisters.

Imaging scans, such as MRI, CT or ultrasound scans, may be used to identify any internal bleeds, for instance, inside a joint or head.

There are two main methods of treatment – preventative (prophylactic) and on demand treatment.

Preventative treatment aims to replace the missing or reduced Factor IX with a manmade substitute. This is given regularly as an injection, into a vein or when young often into a central venous access device such as an implantable port. Families learn to give injections at home which is less disruptive to family life. Prophylaxis is needed for all children with severe haemophilia and is recommended for all children with moderate haemophilia. For children with severe haemophilia, prophylaxis will be offered within a few weeks of birth. People with mild Haemophilia B, that is they have some Factor IX present in the blood, may not need preventative treatment.

On demand treatment is given following an injury or as part of planning surgery. This injection aims to boost the Factor IX. It is used on a temporary basis to reduce the side effects of bleeding following an injury or during surgery. There are other measures that can help reduce the effect of a bleed – read our information sheet ‘Managing bleeds’ for further information. Physiotherapy will usually be needed following a bleed – this may involve giving walking aids or splints, exercises and tailored physical activity guidance to optimise a full recovery.

Development of ‘inhibitors’ that mean the body fights off Factor IX injections can be a problem for people with Haemophilia B. They can have a severe allergic reaction (anaphylaxis) so the initial injection should always be done in a specialist centre where support is available if needed.

It is important that people with

Severe Haemophilia B should not use Non-

Steroidal Anti-Inflammatory Drugs (NSAIDs such as ibuprofen) as this greatly increases the risk of bleeding. However, for mild patients an occasional dose for a fever which has not responded to paracetamol can be used. Other methods of pain relief should be used instead. Caution is needed for injections for severe patients– immunisations for instance, may be given subcutaneously (under the skin) rather than intramuscularly (into a muscle) to reduce the risk of a painful bruised swelling (haematoma) developing. Children and young people with Haemophilia B will need regular reviews at their specialist centre to check that they are responding to treatment and not experiencing any side effects. For severe and moderate patients this review will usually involve a check-up from the physiotherapist as well.

Children and young people with Haemophilia B have a normal lifespan. Some activities may need to be avoided – such as contact sports that carry a high risk of head injury for instance – but most day to day activities will cause few problems.

Long term effects include the development of ‘inhibitors’, that is, the body no longer responds to the Factor IX injections. This will be checked regularly as part of the review process and can be treated with additional injections.

It may be advisable to wear a medical identity necklace or bracelet to alert health care professionals about having Haemophilia B – details are available via the support organisation. Any surgery will need careful planning in advance so it is important that all health care professionals involved are aware.

As Haemophilia B is a genetic condition that can be passed on from parent to child, it is usual to have genetic counselling before planning a family, both for affected individuals and unaffected carriers.

Children and young people with Haemophilia B will need life-long monitoring and treatment, so as your child approaches their teenage years, we will start to talk to them about getting ready to move on to adult health services. This is a planned process so that they become more independent as they grow older and able to manage their own health.