Rhesus disease

Rhesus disease is caused by a specific mix of blood types between a pregnant mother and her unborn baby. Rhesus disease is only possible if:

• the mother is rhesus-negative (RhD negative),
• the baby is rhesus-positive (RhD positive), and
• sensitisation (see below) has previously occurred.

Blood types

There are several different types of human blood. The four main blood groups are:

• Blood group A,
• Blood group B,
• Blood group AB, and
• Blood group O.

Each of these blood groups can either be:

• RhD positive, or
• RhD negative.

Whether someone is RhD positive or RhD negative is determined by the presence of the rhesus D antigen (RhD). An antigen is a protein molecule that is found in your blood (see below). People who have this antigen are RhD positive, and those without it are RhD negative. In the UK, around 85% of the population are RhD positive.

Blood types are inherited

Your blood type depends on the genes that you inherit from your parents. Whether you are RhD positive or negative depends on how many copies of the D antigen you have inherited. For example, you could inherit one copy of the D antigen from your mother, or father, or a copy from both of them, or none at all.

You will be RhD positive if you have inherited either a single copy of the D antigen (called heterozygote Dd) from one of your parents, or two copies (called homozygote DD) from both of your parents. To be RhD negative, you must have inherited no copies of this gene (called homozygote dd).

If a woman who is RhD negative (homozygote dd) has a RhD positive male partner (heterozygote Dd, or homozygote DD) there is a chance that their baby will be RhD positive.

If the male partner has two copies of the D antigen (homozygote DD), the baby will definitely inherit one copy of the D antigen and will be RhD positive.

If the male partner has one copy of the D antigen (heterozygote Dd), there is a 50% chance that the baby will be RhD positive, and a 50% chance that they will be RhD negative. A RhD negative baby will not get rhesus disease.

If your blood is mixed with blood of a different type, your blood will react to it. Each blood type contains different antigens, and in response to antigens from a different blood type, your blood will produce antibodies.

Antigens and antibodies

Antigens are protein molecules that are found on the surface of red blood cells, in the plasma. (Plasma is the liquid which makes up your blood. It contains proteins, nutrients, hormones, waste products and water). Blood groups are identified by the antigens and antibodies that are present in the blood.

Antibodies are your body's natural defence against any foreign antigens that enter your blood. An antibody is a protein that is produced by the body to neutralise or destroy disease-carrying organisms and toxins. If your blood comes into contact with blood that carries different antigens, your body will produce antibodies to those antigens. The antibodies will destroy the foreign blood cells.

The first time your blood comes into contact with another type of blood, and has this response, it is called sensitisation. 

Sensitisation

A RhD positive baby will only have rhesus disease if the RhD negative mother has been sensitised to RhD positive blood. 

Sensitisation describes the process where a mother who is RhD negative is exposed to RhD positive blood for the first time, and has an immune response to it. An immune response occurs when the body reacts to something that it believes to be a threat.

During the immune response, the woman’s body recognises that the RhD positive blood cells are foreign (not part of her blood) and prepares to attack them. Her body does this by designing a specific antibody to target the D antigens in the RhD positive blood cells. Once the design is ready, her body can start producing the antibody.

During sensitisation, the mother’s body recognises the threat and starts to design the antibody. However, at this stage there will probably not be enough time to start producing the antibody before the RhD positive blood is naturally filtered out of her system. Therefore, during sensitisation, it is unlikely that any foreign blood cells will actually be destroyed by the antibodies.

The next time RhD positive blood cells enter the woman’s blood, the design will be ready and the correct antibodies can be produced straight away. This time, enough antibodies will be produced to start destroying the foreign blood cells.

How does sensitisation occur?

The most likely time that RhD positive blood cells could have entered the mother’s blood is during an earlier pregnancy with a baby who was RhD positive.

During pregnancy, sensitisation can happen in a number of ways. These are listed below.

• Small numbers of foetal blood cells cross into the mother’s blood during a normal pregnancy. Although the mother and baby have separate circulatory systems, blood cells can cross over, occasionally leading to sensitisation.
• It is likely that the blood of the mother and baby will come into contact during delivery which can lead to sensitisation.
• If there has been bleeding in the pregnancy - for example, during a threatened miscarriage, it may cause sensitisation.
• If an invasive procedure has been necessary during pregnancy - such as amniocentesis, or chorionic villus sampling (CVS), it may cause sensitisation.
• If the mother has had an abdominal injury - for example, in a road traffic accident, it may cause sensitisation.

Sensitisation can also occur after a previous miscarriage, or ectopic pregnancy, or if a RhD negative woman has received a transfusion of RhD positive blood. 

What does sensitisation do?

Sensitisation has no adverse effects on the mother. Providing that she has not previously been sensitised in another way, it is also unlikely to affect the first RhD positive baby that she has.

If sensitisation occurs during the delivery of a woman’s first RhD positive baby, it is unlikely that she will produce enough antibodies to affect the baby before it is delivered. However, if sensitisation has happened earlier, or in a previous pregnancy, RhD positive babies are at risk of developing rhesus disease.

Rhesus disease

After sensitisation, the mother’s blood has a design to produce antibodies to the D antigen that is found in RhD positive blood. If more RhD positive blood cells enter the mother’s circulation - for example, during a future pregnancy - she will make more antibodies. These antibodies may be sufficient to cross the placenta and destroy the baby’s red blood cells while the baby is in the womb. If this occurs, the baby will develop rhesus disease.