- What is haemophilia
- Inheritance of haemophilia
- Lyonization and clotting factor levels
Haemophilia is a rare congenital bleeding disorder that occurs in people with a limited amount of either clotting factor VIII/ 8 (haemophilia A) or clotting factor IX/ 9 (haemophilia B). The severity of the disease will depend on the level of clotting factors present in the body as outlined in the table below.
Severity of haemophilia
Percentage of normal factor activity in blood
Number of international units (IU) per millilitre (ml) of whole blood
less than 1%
less than 0.01 IU
Having haemophilia means that an individual’s body cannot naturally stop the bleeding that occurs once a blood vessel is damaged. These bleeds can be caused both by trauma and stress. If the bleed is not stopped and properly managed it can result in damages to the joints (such as ankles, hips and knees), which can cripple an individual (to the extreme an individual is at risk of losing limbs such as legs and arms) and limit his or her range of movements. Furthermore, intracranial bleeds can be both debilitating and fatal. In recent years, we have still seen reports of deaths in Europe due to untreated intracranial bleeds.
It is important to understand that besides being debilitating and life-threatening, bleeds are also extremely painful. This is why people with haemophilia need to have access to proper pain management.
Haemophilia has a greater impact on people affected by its severe form. This patients’ population needs to constantly have access to treatment and to specialised healthcare services. People with moderate and mild haemophilia may need treatment only if they injure themselves or if they undergo a great deal of stress. They may also need specialised services for dental care and other types of surgery, however in general they are not as affected by the disorder as people with severe haemophilia and are able to live a fairly normal life.
Living with severe haemophilia means that individuals with this condition need to infuse their treatment product several times a week when they are on prophylaxis. The missing factor is administered intravenously either by a medical professional or by the patient him- or herself. Although in most European countries home treatment is possible (this means that individuals can infuse their treatment without the supervision of a medical professional), it is still a time-consuming activity that may have an impact on an individual’s ability to travel, work and take part in social activities. At the moment, people with haemophilia are prescribed one of two treatment regimens: prophylaxis or on-demand. Prophylaxis treatment is generally recommended in children as it considerably reduces the risks of developing bleeds and damaging joints. In recent years, prophylaxis has been recommended also to elderly populations to preserve joints. Currently, for patients with severe haemophilia the recommended trough levels (i.e. the lowest level of coagulation factor present in the body) are set at 1 per cent.
People with haemophilia have access to two types of treatments: plasma-derived or recombinant. Plasma-derived treatment is made from human plasma, while recombinant treatment is produced from live cells such as monoclonal antibodies. Both treatments are effective, although they can vary in costs as recombinant products are often considered more technologically advanced and carry less risks of viral contamination.
Finally, it is also important to know that at the moment approximately 30 per cent of the haemophilia population will develop an inhibitor to their treatment. This means that the body will reject the treatment, leaving the haemophiliac with no treatment solutions. For further information on this, please consult the inhibitors’ section.
Inheritance of haemophilia
Haemophilia is usually inherited, meaning that it is passed on through a parent’s genes. The genes for haemophilia A and haemophilia B are on the X chromosome. For this reason, haemophilia is called an X-linked (or sex-linked) disorder.
However it is estimated that approximately 40 per cent of people with haemophilia have what is called sporadic haemophilia, which means that the condition is caused by a change in the person’s own genes.
The figure below explains how the haemophilia gene is inherited. When the father has haemophilia but the mother does not, none of the sons will have haemophilia while all of the daughters will carry the haemophilia gene. Women who have the haemophilia gene are called carriers. They sometimes show signs of haemophilia and they can pass it on to their children. For each child, there is a 50 per cent chance that a son will have haemophilia and a 50 per cent chance that a daughter will carry the gene.
Women can only inherit haemophilia if their father has haemophilia and their mother is a carrier. This is very uncommon.
A woman who has less than 40 per cent of the normal level of clotting factor is no different from a man with the same factor levels — she has haemophilia.
Some carriers have symptoms of haemophilia even though their clotting factor levels are above 40 per cent. A woman with levels of 40-60 per cent of the normal amount of clotting factor who experiences abnormal bleeding is called a symptomatic carrier.
Lyonization and clotting factor levels
In each cell in a woman’s body, one of the two X chromosomes is turned off or ‘suppressed.’ This process is called ‘lyonisation,’ after Mary Lyon who first described it. Lyonization is a random process that is not fully understood.
If the chromosome that is turned off has the altered gene, that cell will produce clotting factor. If the chromosome with the normal gene is turned off, the cell will not produce clotting factor, or the clotting factor it makes will not work properly.
On average, carriers of haemophilia will have about 50 per cent of the normal amount of clotting factor, because about half of their cells will have the ‘good’ gene turned off. Some carriers have far lower levels of clotting factor.
Back to top
Haemophilia is diagnosed by taking a blood sample and measuring the level of factor activity in the blood.
If the mother is a known carrier of haemophilia, testing can be done before a baby is born. Prenatal diagnosis can be done at 9 to 11 weeks by chorionic villus sampling (CVS) or by foetal blood sampling at a later stage (18 or more weeks). Expecting mothers can also get their blood tested at 7-8 weeks to determine the sex of the baby. If the mother is expecting a girl, she can forego CVS, which reduces risks of miscarriage.
These tests can be done at a haemophilia treatment centre.
You can find more information about haemophilia via the following websites and documents:
- World Federation of Hemophilia
- Haemophilia Central
- Booklet “Introduction to haemophilia” from the Irish Haemophilia Society