Haemophilia B (factor IX, F9 gene): causes, inheritance and care

In haemophilia B the blood lacks enough clotting factor IX (factor 9). The Haemophilia Society notes that it is also known as Christmas Disease, and the NHS says that haemophilia A and B cause the same symptoms: bleeding for a long time after an injury, surgery or a tooth extraction, easy bruising, and joint pain, stiffness and swelling. Symptoms usually begin in early childhood, but sometimes are not noticed until later.

The NHS adds that the less clotting factor a person has, the more severe the symptoms, and that people with severe haemophilia need more treatment and have a higher risk of life-threatening bleeding. Other conditions, such as von Willebrand disease, can look similar, which is why the amount of each clotting factor is measured.

The NHS Genomics Education Programme grades haemophilia B by factor IX activity in the same way as haemophilia A. Below 1% is severe, with a risk of spontaneous joint and muscle bleeding, and rarely bleeding inside the skull in the first months of life. Between 1% and 5% is moderate, and above 5% is mild, where bleeding is usually triggered by trauma and some people notice little more than easy bruising.

A rare variant called haemophilia B Leyden behaves differently: the factor IX level increases with age, so the picture can change as a person grows older. All children with severe haemophilia B need prophylaxis, and prophylaxis is now offered to all children with moderate haemophilia, according to the programme.

Most harmful changes in F9 are single-letter alterations (point mutations, 76.7%), with deletions making up 17.2% and other types fewer than 5%, per the NHS Genomics Education Programme. As in haemophilia A, finding the exact variant helps: some variants are linked to a particular severity and some to a greater chance of inhibitor antibodies against factor IX, which can complicate treatment.

Genetic testing can be aimed at F9 alone or can look at F9 together with other genes that cause bleeding and platelet disorders. The programme says confirmation of diagnosis needs referral to a haemophilia comprehensive care centre, and that any patient with a possible diagnosis, particularly if severe, is referred urgently.

Because the F9 gene is on the X chromosome, men with the altered gene have haemophilia B and women with one altered copy are carriers. A woman who is a carrier gives each child one of her two X chromosomes, so half of her sons are expected to have haemophilia and half of her daughters to be carriers. A father with haemophilia passes his X chromosome to every daughter, who all become carriers, and his Y chromosome to every son, who therefore do not inherit the condition from him.

Carriers can have bleeding symptoms. The NHS Genomics Education Programme says some female carriers have clinically significant bleeding, and in rare situations a carrier can be severely affected when the working copy is silenced. The programme advises that female siblings of affected boys should have factor IX tested in childhood to set a baseline, and that predictive genetic testing for relatives is generally considered in the mid-teens, when they can consent for themselves.

In the programme's account, around one-third of haemophilia B variants are new in the individual, so the absence of a family history does not exclude the condition.

In families with a known history, cord blood testing at birth can be planned before delivery, according to the NHS Genomics Education Programme. The NHS says a GP can refer anyone at risk of having a child with haemophilia to a genetic counsellor to discuss the risks and options, with tests available before, during and after pregnancy. These can include a carrier test, a blood test in early pregnancy to check the baby's sex, chorionic villus sampling or amniocentesis, and a blood test from the baby after birth.

The programme also describes non-invasive fetal sexing from about 7 to 8 weeks, followed by invasive testing if the baby is male, and IVF with pre-implantation genetic testing for those who wish to avoid transferring an affected embryo. Carrier mothers should have their pregnancy managed jointly with the haemophilia service and the local obstetric team, including plans for the place and mode of delivery.

Treatment replaces the missing factor. The NHS says clotting factor is given by injection and that for haemophilia B, as for A, preventive injections up to three times a week are usual in severe disease, often given at home after training, while mild and moderate haemophilia are generally treated on demand and before surgery or dental work. The NHS Genomics Education Programme adds that options for prophylaxis include factor IX-based treatment and that care involves a haemophilia consultant, education about recognising bleeds, and regular physiotherapy.

The Haemophilia Society says that with modern treatment a child with haemophilia has every chance of growing up as an active, fit child who can take part fully in family, school and working life, and describes the outlook in the UK as the best it has been. The NHS says that with treatment people usually have a normal life expectancy, although some develop complications. Any head injury, serious cut, black or bloody stool, or sudden severe headache with confusion needs 999 or A&E, according to the NHS.