Presentation: Patient with microcytic anaemia with normal ferritin

A well 27-year-old woman is unexpectedly found to have an Hb level of 110g/L (normal range 120–160g/L) with a mean corpuscular volume (MCV) of 70fL (normal range 80–100fL). She is keen to ensure that she is fit and healthy as she is planning a pregnancy. Her repeat full blood count is similar, and her ferritin is normal at 78ng/ml.

• Individuals presenting with persistent microcytic anaemia with normal ferritin and iron studies may have an underlying haemoglobinopathy such as thalassaemia trait or sickle cell disease.
• These individuals are more commonly carriers, as affected individuals usually present earlier in life and more acutely.
• Most haemoglobinopathies are autosomal recessive and carriers are usually well, although they are at risk of having affected children depending on the carrier status of the other parent.
• If two carriers of an autosomal recessive condition have a child together, there is a one-in-four (25%) chance of that child being affected.
• Flags for an underlying genetic diagnosis include either:
  • Mediterranean, Arabic, Asian or African ancestry (although haemoglobinopathies can occur in all ethnic groups);
  • family history of haemoglobinopathy; or
  • persistent microcytic anaemia with normal ferritin and iron studies.

• Send samples of the patient’s blood for haemoglobin electrophoresis.
• If carrier status for thalassaemia or a haemoglobin variant is confirmed, then counsel the patient regarding autosomal recessive inheritance, risks and reproductive options (which include prenatal diagnosis and preimplantation genetic testing).
• If the individual is planning a pregnancy, advise that their partner seeks carrier testing via primary care. Should both partners in the couple receive a confirmed carrier status for thalassaemia or a haemoglobin variant then a clinical genetics referral for genomic counselling is warranted.
• In these patients, oral iron supplementation may not be necessary or beneficial).
• If a benign haemoglobin condition (such as Hb C disease, Hb D disease or Hb E disease) is identified, haematological advice and/or referral to the relevant specialty is advised (advice may be included with the result report).
• More rarely, sickle cell disease or beta thalassaemia may be diagnosed, requiring urgent haematological or paediatrics referral.

For clinicians

• National Institute of Diabetes and Digestive and Kidney Diseases: Sickle cell trait and other hemoglobinopathies and diabetes
• NHS England: National Genomic Test Directory
• NHS England: NHS Sickle cell and thalassaemia: screening handbook

References:

• Ryan K, Bain BJ, Worthington D and others. ‘Significant haemoglobinopathies: Guidelines for screening and diagnosis’. British Journal of Haematology 2010: volume 149, issue 1, pages 35–49. DOI: 10.1111/j.1365-2141.2009.08054.x

For patients

• NHS England: Thalassaemia
• NHS Health A to Z: Sickle cell disease
• Sickle Cell Society
• UK Thalassaemia Society