Improving blood matching for transfusions in patients with sickle cell disorder

The transfusion of red blood cells may be a one-off event, or it may be required every few weeks over many years, for example for people with an inherited  anaemia such as sickle cell disorder. Here Dr Sara Trompeter, a consultant haematologist, discusses the challenges in matching blood for transfusions  and advances in red cell genotyping through the Haem-Match project.

Matching blood

Red blood cells – the cells that carry oxygen around the body – have labels on their surfaces, known as antigens or blood groups, which we inherit genetically from our parents. Blood is selected for transfusion according to the blood groups of the donor and the blood group of the recipient – we call this ‘matching’. There are over 2 million units of blood donated a year in the UK. There are over 200 blood groups so matching for everything every time is not feasible. Currently, we routinely provide blood matched for the ABO blood groups and also for RhD (a protein found on the surface of red blood cells; previously also referred to as Rhesus).

The consequences of unmatched blood groups

For most people undergoing a blood transfusion, provided they are ABO and RhD matched, there are no complications. However, a patient may form an antibody against a blood group if the red cells of the donor have an antigen that is ‘foreign’ to the patient (i.e. if the red cells of the donor have a blood group that the red cells of the recipient do not). This is known as alloimmunisation.

Alloimmunisation can be dangerous, because if the patient is transfused subsequently with blood containing the antigen that caused the antibody to form, there is a risk that the immune system of the patient will attack the transfused cells, causing a haemolytic reaction that can be fatal. We know that some people who receive transfusions (such as those with sickle cell disorder and thalassaemia) are more likely to form antibodies than patients with a condition requiring a one-off transfusion.

When [Ama] was pregnant … there were only two units of blood available for her nationally. If she were to have had a serious sickle-related complication, she would have likely needed at least eight units of blood to treat her.

To reduce the risk of antibody formation, blood for regularly transfused patients is matched at present by considering other Rh antigens, for example C, c, E, e and the K blood groups in addition to the A, B, O and D blood groups. Despite this, around 17% of such people do make antibodies to the other blood groups that we do not match and many will have severe transfusion reactions. This can result in real difficulty in getting blood for them.

Ama’s story

Ama has sickle cell disorder and developed antibodies following transfusion. When she was pregnant in 2018 there were only two units of blood available for her nationally. If she were to have had a serious sickle-related complication such as a chest syndrome, she would have likely needed at least eight units of blood to treat her. We met with Ama and had a conversation about the impact of alloimmunisation on her. She spoke candidly about the anxiety that she experienced during her pregnancy. She discussed the enormous lengths the clinical and laboratory staff in the hospital and NHS Blood and Transplant (NHSBT) – the national blood service for England – went to ensure that suitable blood was made available for her should she have needed it.

Ama spoke about her hopes … for her children who also have sickle cell disorder. Ama is hopeful that they might not form antibodies and be in such a vulnerable position as herself. This is a major aim of Haem-Match.

We spoke about the rare donor panel – a group of donors with rare blood groups who are supported by NHSBT to donate, sometimes in an emergency – whose selflessness she was particularly touched by. The National Frozen Blood Bank in Liverpool and teams in NHSBT such as the red cell immuno-haematology (RCI) teams and the International Blood Group Reference Laboratory (IBGRL) undertake testing and research to support those who are difficult to transfuse. Ama spoke about her hopes for the future, particularly for her children who also have sickle cell disorder. Ama is hopeful that they might not form antibodies and be in such a vulnerable position as herself. This is a major aim of our research project Haem-Match.

What is Haem-Match?

Haem-Match aims to provide blood for transfusion that is more precisely matched to patients’ blood groups, known as extended (red cell antigen) matching. In doing so, we can reduce the risk of harm caused by transfusion (for example antibody formation, alloimmunisation and transfusion reactions), streamline the allocation of precisely genetically matched units to patients with complicated transfusion needs, and reduce waste and improve efficiency in the collection and allocation of blood units.

Although the project initially focuses on reducing the risk of blood transfusion treatment for people with sickle cell disorder, we hope to expand this to people with other transfusion-dependent anaemias such as thalassaemia and myelodysplastic syndrome.