Haemophilia A

Haemophilia A (Factor VIII deficiency) is the most well-known type of clotting disorder. 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 A 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 A (Factor VIII deficiency) is the most well-known type of clotting disorder. The specific coagulation factor that is missing or reduced in people with Haemophilia A is Factor VIII. The severity of symptoms ranges from mild to severe depending on the amount of Factor VIII present in the blood and its activity.

Haemophilia A is caused by a mutation/variant

(change) on the Factor VIII gene on the

X-chromosome (specifically at location Xq28), 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 A 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 FVIII levels)
• 25 per cent chance of the child being an unaffected boy
• 25 per cent chance of the child being an affected boy.

Although Haemophilia A is an X-linked condition and therefore mainly affects boys, it can occur in females in a milder form. Carrier females may have mildly low levels and mild bleeding problems, such as heavy periods, but these are not usually severe enough to need factor 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 VIII in the blood. Children with little or no Factor VIII may start to show symptoms soon after birth, whereas those with some functioning Factor VIII may not show symptoms until later, often following surgery or injury.

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

Haemophilia A 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 A 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 for 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 (prophylaxis) and on demand treatment to treat bleeds.

Prophylaxis aims to replace the missing or reduced Factor VIII with a man-made substitute. There are two main types of prophylaxis: factor VIII and non-factor therapy (Hemlibra /Emicizumab - currently only available for patients with severe haemophilia). Factor VIII 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. Hemlibra is given as a subcutaneous injection.

The Haemophilia team will help you decide which approach is right for your child. 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 A, who have some Factor VIII 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 VIII. 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.

Children with mild haemophilia who are over 5 years of age can sometimes have an injection called DDAVP or desmopressin to boost their body’s own Factor VIII level. A medication called tranexamic acid can also be useful for minor symptoms in some mildly affected patients or as additional treatment together with factor for some children.

Development of ‘inhibitors’ that mean the body fights off Factor VIII injections can be a problem for people with Haemophilia A. This is more common for children with severe Haemophilia A. This will be checked regularly at review appointments. If inhibitors develop, additional injections will be needed.

It is important that people with severe Haemophilia A 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. In general, other methods of pain relief should be used instead. Caution is needed for injections for severe patient’s 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 A 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 A 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 VIII 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 A – 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 A is a genetic condition that can be passed on from parent to child, it is usual to have genetic counselling from a haemophilia service before planning a family, both for affected individuals and unaffected carriers.

Children and young people with Haemophilia A 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.