NHS Sickle Cell and Thalassaemia Screening Programme
Sickle cell and thalassaemia are the commonest recessively inherited disorders in the UK. In the case of sickle cell disease, there are approximately 240,000 healthy carriers and >12500 affected people in the UK.
With increasing numbers of ethnically ‘mixed’ couples, offering screening only to certain ethnic groups is becoming a less reliable way of identifying affected babies. For this reason a linked antenatal and newborn screening programme has been introduced.
Screening for sickle cell disease is now offered to all newborn babies together with targeted antenatal screening for sickle cell disease based on ethnicity factors.
Screening for thalassaemia is offered to all women antenatally.
Adult haemoglobin (HbA) is a complex protein that consists of two alpha and two beta globin chains. People with sickle cell disease produce a structural variant of the haemoglobin protein (HbS). This leads to abnormal sickle shaped red blood cells which can occlude small blood vessels particularly at times of metabolic stress.
Usually people with sickle cell disease are homozygous for the HbS gene and produce only HbSS but other haemoglobins in combination with HbS can sometimes cause a sickle cell disorder, for example HbSC, HbS/D. Carriers of sickle cell disease are usually clinically unaffected.
Thalassaemia is due to an imbalance in globin chain synthesis. Production of either the alpha or the beta chains of haemoglobin may be reduced, resulting in alpha- or beta-thalassaemia respectively. The red blood cells contain a much reduced amount of haemoglobin, causing profound anaemia.
Individuals with beta thalassaemia major require regular blood transfusions from about 9 months of age with iron chelation therapy to remove excess iron. Bone marrow transplant may be feasible.
Alpha thalassaemia major causes severe anaemia in the fetus during pregnancy leading to stillbirth or neonatal death (hydrops fetalis).
Alpha thalassaemia intermedia (haemoglobin H disease) causes moderate anaemia with little pathology in most cases. There are other haemoglobin variants which will be picked up by screening, some of which are of no clinical significance.
Newborn testing
- All newborns babies are now offered screening for sickle cell as part of the Newborn Blood Spot Programme (formerly known as the Guthrie test). This provides an additional screen to the antenatal testing of the parents. It will pick up those affected babies whose parents may have avoided antenatal testing for whatever reason.
- Every year 300 babies are born in England with sickle cell disorders. It is therefore the commonest genetic disorder in England. Early detection in babies allows treatment to commence with penicillin and Prevenar vaccine to be given at 3 months of age in order to protect against pneumococcal sepsis.
- The analytical procedures used will detect sickle cell carriers, thalassaemia and some other clinically benign haemoglobin variants. It will not detect B-thalassaemia carriers.
Antenatal testing
- As part of antenatal screening in England, all pregnant women are screened for thalassaemias (using routine blood indices).
- In high prevalence areas (Newcastle within the Northern Region), every woman is offered screening to see if she is a carrier of a sickle cell or other haemoglobin variant. In lower prevalence areas, this test is offered according to ancestry (using a family origin questionnaire).
- The antenatal screening programme is designed to identify most carriers for sickle cell disease, thalassaemia and related disorders. It will not identify every couple at risk for every haemoglobinopathy.
- When a pregnant woman is found to be a carrier, the baby’s father should be offered testing as soon as possible.
- Early is best. The earlier in pregnancy an ‘at risk’ couple (where both parents are carriers) are identified – preferably well within the first trimester – the more time they have to be referred, and to make choices about the pregnancy.
- Sickle cell and thalassaemia are both recessive conditions. If a couple who are both healthy carriers decide to have children, there is a 1 in 4 chance with each pregnancy that the child will have a sickle cell or thalassaemia disorder.
- ‘At risk’ couples may choose to undergo prenatal diagnosis via CVS or amniocentesis. They may, or may not, subsequently choose to terminate an affected pregnancy.
Pitfalls to avoid
Do not assume that sickle cell or thalassaemia are confined to a particular ethnic group. They may occur in any ethnic group.
- Antenatal screening for thalassaemia uses blood indices. A low mean haemoglobin detected on a full blood count may mean iron deficiency, or thalassaemia carrier status, or both. It may be appropriate to simultaneously investigate pregnant women for iron deficiency using ferritin or zinc protoporphyrin, but there is no justification for delaying the investigation of haemoglobinopathies whilst treating iron deficiency, as this will delay the process of identifying at risk carrier couples who could be offered prenatal diagnosis.
- Never accept a diagnosis (e.g carrier / not a carrier) on hearsay. All decisions should be based on evidence from seeing the test result, or a card previously issued to the patient.
