Genetics, family screening, and carrier testing

Bleeding disorders are usually inherited conditions, which means that they result from changes to genes (also known as mutations) that are present from birth.

Genes are the unique sets of ‘instructions’ that make each of us different. There are many thousands of different genes, each carrying a different ‘instruction’. Genes affect how we look and the way each cell (or ‘building block’) of the body works. They can tell your body to make specific proteins, such as clotting factors.

Genes lie on tiny structures called chromosomes, like beads threaded onto a string. Each chromosome contains thousands of genes. We have 2 copies of each chromosome (and so 2 copies of every gene). We each inherit 1 copy from each of our parents. When we have children, we pass on only 1 copy of each of our chromosomes.

Sometimes 1 changed copy of a gene is enough to cause a bleeding disorder. This is known as autosomal dominant inheritance. Most types of von Willebrand disease follow this pattern.

Other types of bleeding disorder, such as Glanzmann’s thrombasthenia, need 2 changed copies of the gene. This is known as autosomal recessive inheritance. In this situation, if someone carries a changed gene but does not have clinical features of the condition, they are known as a carrier of the condition.

Usually genetic changes that cause bleeding disorders are inherited from the affected person’s parents. This is not always the case though. Depending on the condition, a parent could:

• carry the genetic change and be affected by the bleeding disorder
• be a carrier without symptoms
• not carry any genetic change, and be unaffected

Siblings and children of an affected person may also have inherited the changed gene and be affected, or be carriers.

It is important that the relevant family members are aware of this risk and are tested. We can help with this. This process is called genetic counselling. If possible, and if you agree, we try and determine the genetic change responsible for your bleeding disorder. This involves a simple blood test.

Family screening

This is when relatives of someone with a bleeding disorder are tested to see if they are also affected. This usually involves a review in clinic and a blood test. We can check whether they have the same bleeding condition as the affected person (for example, a low clotting-factor level). If the genetic cause is known, we can test for the genetic mutation too. We often need a referral from the relative’s GP to offer a family screening appointment.

Carrier testing

Haemophilia A and B are X-linked conditions. This means that the genetic change is on the X chromosome. Because men only have 1 copy of the X chromosome but women have 2, men are more commonly affected by haemophilia than women.

Chances of being affected

If a man has a haemophilia mutation on his X chromosome, he will be affected by haemophilia. If a woman has a haemophilia mutation on 1 of her 2 X chromosomes, she is known as a haemophilia carrier. Female haemophilia carriers sometimes have low levels of factor VIII (F8) or IX (F9) themselves, but not normally as low as their affected male relatives.

Being a carrier of a bleeding disorder means there is a chance of having an affected child. For female haemophilia carriers there is a:

• 1 in 2 (50%) chance of a son being affected by haemophilia
• 1 in 2 (50%) chance of a daughter being a haemophilia carrier

Outcomes of carrier testing

In haemophilia A and B, and some other rare bleeding disorders, it is important to arrange carrier testing.

In haemophilia, some female relatives of affected people might carry the haemophilia gene, but not know about it. By measuring factor levels and doing genetic testing on blood, female relatives who are haemophilia carriers can be identified. This means that, if they also have low FVIII or FIX levels and an increased chance of bleeding, this can be identified.

They can also be counselled about what this might mean for their own children, including the chance of having an affected son or carrier daughter. We might need a referral from the relative’s GP to offer a carrier testing appointment.

Support and more information

The Haemophilia Society has more information about genetic causes of bleeding disorders and genetic testing.

The NHS also has information about genetic testing.