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Clinical clangers: ‘Your small red blood cells indicate you’re anaemic, so I’m prescribing iron tablets’

Continuing our series on clinical scenarios that can be mishandled in primary care, Dr Claire Davies considers a finding of abnormal red blood cells

Dr Morse is filing his blood results on Mrs Rahman when he notices an FBC that was requested by the locum doctor. Most indices are normal, but the mean corpuscular volume (MCV) is 68. He notes that the mean corpuscular haemoglobin (MCH) is also low. Given the patient’s history of menorrhagia, he arranges a trial of oral iron treatment and a follow-up appointment in three weeks’ time.

The reality
Mrs Rahman’s blood indices may be due to an iron deficiency, but could also be the result of an underlying haemoglobinopathy trait.1 

With increasing global population migration, inherited disorders of globin synthesis such as sickle disease and thalassaemias have become common in the UK population. 

Testing should be arranged for haemoglobin electrophoresis and sickle trait as well as ferritin.  

The issue
It is important to identify whether the aetiology is iron deficiency or an inherited haemoglobinopathy trait. Inappropriate treatment with oral iron carries risks of iron overload or side-effects. 

Patients with low ferritin can be treated for iron deficiency. Patients identified as haemoglobinopathy carriers should be offered pre-conception advice. If both parents are sickle trait or ß-thalassaemia carriers, the child has a 25% chance of inheriting both genes to develop the full-blown disease.  

In addition, while sickle trait is generally thought of as benign, carriers can experience sickle crises under conditions of general anaesthetic, extreme dehydration or lack of oxygen – for example, at high altitude. Sickle trait is also associated with renal papillary necrosis, chronic kidney disease and renal medullary carcinoma.  

The evidence 
A low MCV may commonly be presumed to be due to iron deficiency, which affects around 2-5% of adult men and post-menopausal women in developed countries.2

However, inherited traits of haemoglobinopathies are also very common, particularly in some regions of the UK where antenatal screening prevalence is 2% of samples or greater.3 The National Haemoglobinopathy Register holds a record of 11,000 patients with sickle cell disease, but registration is voluntary so the true number affected is likely to be higher. Around 1,000 pregnancies per year are affected by sickle cell disease.4 Globally, 1.5% of the world’s population are ß-thalassaemia carriers.5

Avoiding a clanger 
Bear in mind this blood picture can have other causes than iron deficiency. The MCV may be around 70 or lower in haemoglobinopathy traits, although this is by no means universal. MCH is also often low. 

It is important to screen for haemoglobinopathy in high-risk groups. Affected ethnic groups include black (black African, black British and black Caribbean plus central or southern American of black or partial black ethnicity), North African, South and South East Asian people, as well as some southern Europeans, for example people from Greece and parts of Southern Italy.

Even if the history fits with iron deficiency, we should always check ferritin before managing as iron deficiency, as recommended by NICE.6

A normal MCV does not exclude haemoglobinopathy traits in high-prevalence groups. Other, more rare causes of a low MCV include lead poisoning and sideroblastic anaemia.

Key points

  • A finding of a low MCV should always prompt further checking of ferritin to test for iron deficiency
  • Haemoglobinopathy screening is indicated in at-risk groups with low MCV
  • The UK prevalence of haemoglobinopathy may be 2% or greater depending on the ethnic composition of the area
  • It is important to identify haemoglobinopathy traits even in asymptomatic patients, to inform future healthcare decisions and allow for preconception advice

Dr Claire Davies is a GP in east London