Guidance

Introduction

Updated 10 October 2024

Applies to England

This guidance describes the requirements for laboratories involved in antenatal screening and referral of antenatal samples to DNA laboratories.

Laboratories must check this section information frequently. The guidance and requirements described relate to a screening programme, not a diagnostic service.

Sickle cell and thalassaemia (SCT) screening laboratories must:

• be accredited by the UK Accreditation Service (UKAS) to ISO Medical laboratories – requirements for quality and competence (ISO 15189:2012)
• meet screening programme quality assurance (QA) requirements mapped to ISO 15189:2012
• participate in external quality assurance (EQA) schemes accredited to ISO Conformity assessment. General requirements for proficiency testing schemes (ISO 17043:2010)
• use ISO 15189:2012 accredited reference laboratories

UKAS looks at ISO 15189:2012 and the screening requirements on behalf of regional screening quality assurance services (SQAS) and the national screening programme.

NHS population screening explained sets out the general principles of screening.

1. Related documents

This handbook for antenatal laboratories is part of a suite of documents.

The SCT screening programme handbook provides operational guidance and information for all practitioners involved in screening.

The SCT screening pathway requirements specification provides an overview of SCT screening by describing what should happen at each stage of the end-to-end pathway.

The SCT screening programme standards define a set of standards providers have to meet to make sure local SCT screening services are safe and effective.

Providers must comply with national guidance for the management of safety concerns and incidents in screening programmes and NHS England guidance for the management of serious incidents.

The British Committee for Standards in Haematology (BCSH) has published guidance about screening^{[footnote 1]}.

2. Haemoglobinopathies

Haemoglobinopathies are a heterogeneous group of more than 1,000 mutations, which are categorised into 2 main groups:

• haemoglobin variants
• thalassaemias

The haemoglobin variants arise from an alteration in the globin protein structure. The thalassaemias arise from inadequate production of structurally normal globin. There are also thalassaemic haemoglobinopathies that are produced when a structurally abnormal haemoglobin is synthesised at a reduced rate, for example haemoglobin E (HbE).

The frequency of different haemoglobinopathies varies in different ethnic groups and certain haemoglobinopathies are often associated with a family history. It is important to remember that no haemoglobinopathy is exclusive to any single ethnic group, so all individuals are theoretically at risk.

It is not unusual for people to inherit more than one haemoglobin mutation. Many haemoglobin mutations have no associated clinical significance. Others are associated with severe morbidity and mortality, most notably sickle cell disease and beta (β) thalassaemia major. Changing treatment options including new drug regimes, improved bone marrow transplant (BMT) protocols and gene therapy have the potential to significantly improve patient outcomes. Carriers of a haemoglobin mutation are usually asymptomatic.

3. Sickle cell disease

Sickle haemoglobin (HbS) is a haemoglobin variant in which valine replaces glutamic acid, which is the sixth amino acid in the β globin chain. Other much rarer haemoglobins are reported that have this same glutamic acid to valine substitution, but also an additional substitution in cis. All these variants will cause sickle cell disease in the situations described below for HbS.

Sickle cell disease results from the inheritance of certain genotypes, including:

• homozygosity for HbS (sickle cell anaemia)
• compound heterozygosity for HbS and an interacting mutation, such as HbC (Hb SC disease)
• β thalassaemia (Hb S/β thalassaemia)

The sickling conditions are associated with severe life-threatening vaso-occlusive crises, overwhelming sepsis, splenic sequestration, aplastic crises, stroke, priapism, pulmonary hypertension, proliferative retinopathy, chronic organ damage and avascular necrosis of the hips and shoulders.

4. Beta thalassaemia major

Beta thalassaemias are a group of hereditary conditions that result in reduced (β⁺) or absent (β⁰) synthesis of β globin chains. These are an essential component of the main adult haemoglobin, HbA.

Beta thalassaemias are usually caused by point mutations, small insertions or deletions and, less frequently, large deletions of the β globin gene located on chromosome 11. Inheritance is predominantly autosomal recessive although some dominant mutations have been reported.

Mutation type and inheritance patterns result in variable phenotypes, which range from severe transfusion-dependent anaemia (beta thalassaemia major) to clinically asymptomatic carriers. Lifelong transfusion treatment has associated complications of iron overload, including endocrine dysfunction, cardiomyopathy, liver fibrosis and cirrhosis. A demanding daily regime of therapy with iron chelators that enable iron excretion from the body is required to treat these complications. Insufficient red cell replacement results in symptoms of anaemia, jaundice, poor growth and muscular development and skeletal changes from expansion of the bone marrow due to extramedullary haemopoiesis.

Thalassaemia intermedia is a highly variable condition. Although some cases are transfusion-dependent it is usually a less severe disease than β thalassaemia major.

5. Screening support service

Laboratories may have questions about screening policy or interpretation of results that cannot be answered easily by reference to this handbook or textbooks.

Oxford University Hospitals NHS Trust provides a support service for screening laboratories via designated telephone helplines and secure email. The national SCT screening programme commissions this service, which supports both antenatal and newborn screening inquiries.

6. Education of laboratory screening staff

Recommended e-learning for screening laboratory based staff is SCT Laboratory module – part 1, part 2 and a quiz on elearning for healthcare.

Recommended education for bench level staff and haematology laboratory managers is attendance at NHS SCT laboratory workshops.

Telephone: 01865 572 769
Email: [email protected]

1. Ryan K, Bain B, Worthington D, James J, Plews D, Mason A, et al. Significant haemoglobinopathies: guidelines for screening and diagnosis. British Journal of Haematology 2010: volume 149, pages 35 to 49 ↩