CHAPTER 1
Iron Deficiency Anaemia

Catherine Booth1 and Drew Provan2

1 Barts Health NHS Trust; NHS Blood and Transplant, London, UK

2 Department of Haematology, Barts Health NHS Trust; London School of Medicine & Dentistry, London, UK

OVERVIEW

• Iron deficiency is the commonest cause of anaemia worldwide and is frequently seen in general practice.
• The anaemia of iron deficiency is caused by defective synthesis of haemoglobin, resulting in red cells that are smaller than normal (microcytic) and contain reduced amounts of haemoglobin (hypochromic).

Iron metabolism

Iron has a pivotal role in many metabolic processes, and the average adult contains 3-5 g of iron, of which two-thirds is in the oxygen-carrying molecule haemoglobin (Hb).

A normal Western diet provides about 15 mg of iron daily, of which 5-10% is absorbed (~1 mg), principally in the duodenum and upper jejunum, where the acidic conditions help the absorption of iron in the ferrous form. Absorption is helped by the presence of other reducing substances, such as hydrochloric acid and ascorbic acid. The body has the capacity to increase its iron absorption in the face of increased demand - for example, in pregnancy, lactation, growth spurts and iron deficiency (Table 1.1).

Once absorbed from the bowel, iron is transported across the mucosal cell to the blood, where it is carried by the protein transferrin to developing red cells in the bone marrow. Iron stores comprise ferritin, a labile and readily accessible source of iron, and haemosiderin, an insoluble form found predominantly in macrophages.

About 1 mg of iron a day is lost from the body in urine, faeces, sweat and cells shed from the skin and gastrointestinal tract. Menstrual losses of an additional 20 mg a month and the increased requirements of pregnancy (500-1000 mg) contribute to the higher incidence of iron deficiency in women of reproductive age (Box 1.1).

Clinical features of iron deficiency

The symptoms accompanying iron deficiency depend on how rapidly the anaemia develops. In cases of chronic, slow blood loss, the body adapts to the increasing anaemia, and patients can often tolerate extremely low concentrations of haemoglobin - for example, <70 g/l - with remarkably few symptoms. Most patients complain of increasing lethargy and dyspnoea. More unusual symptoms are headaches, tinnitus, taste disturbance and restless leg syndrome. Pica (a desire to eat non-food substances) and, most characteristically, pagophagia (abnormal consumption of ice) are uncommon but well-described and resolve promptly with iron replacement. In children, chronic iron deficiency anaemia can lead to impaired psychomotor and cognitive development.

Table 1.1 Daily dietary iron requirements.

On examination, several skin, nail, hair and other epithelial changes may be seen in chronic iron deficiency. Atrophy of the skin occurs in about a third of patients, and hair thinning may be particularly noted in young women. Nails may become brittle, but the classic finding of koilonychia (spoon-shaped nails) is unlikely to be seen in clinical practice in higher-income countries. Patients may also complain of angular stomatitis, in which painful cracks appear at the angle of the mouth, sometimes accompanied by glossitis. Although uncommon, oesophageal and pharyngeal webs can be a feature of iron deficiency anaemia (consider this in middle-aged women presenting with dysphagia). These changes are believed to be due to a reduction in the iron-containing enzymes in the epithelium and gastrointestinal tract. Few of these epithelial changes are seen in modern practice and are of limited diagnostic value.

Tachycardia and cardiac failure may occur with severe anaemia irrespective of cause, and in such cases, prompt remedial action should be taken.

When iron deficiency is confirmed, a full clinical history, including leading questions on possible gastrointestinal blood loss or malabsorption (as in, for example, coeliac disease), should be obtained. Menstrual losses should be assessed, and the importance of dietary factors and regular blood donation should not be overlooked (Figure 1.1).

Box 1.1 Causes of iron deficiency anaemia.

Most iron deficiency anaemia is the result of blood loss, especially in affluent countries.

Diet alone is seldom the sole cause of iron deficiency anaemia in adults in Britain except when it prevents an adequate response to a physiological challenge - as in pregnancy, for example. In children, by contrast, diet is a key factor, particularly in infants slow to wean (e.g. by 6 months) or those fed cow's milk (which has low iron content and poor bioavailability) before 12 months.

A state of 'functional iron deficiency' is common in patients with chronic inflammatory conditions and often co-exists with anaemia or chronic disease. Total body iron may be normal, but iron stores cannot be mobilized for making new red cells due to changes in metabolic or transport pathways.

Figure 1.1 Diagnosis and investigation of iron-deficiency anaemia.

Laboratory investigations

A full blood count and film should be assessed (Box 1.2). These will confirm the anaemia, and recognising the indices of iron deficiency is usually straightforward (reduced haemoglobin concentration, reduced mean cell volume (MCV), reduced mean cell haemoglobin (MCH), reduced mean cell haemoglobin concentration). It is worth noting that a reduction in haemoglobin concentration is a late feature of iron deficiency, and in up to 40% of cases, MCV may be normal. The first change may be an increase in the red cell distribution width. There may be a reactive thrombocytosis. Some modern analysers will determine the percentage of hypochromic red cells or the haemoglobin content of reticulocytes, both of which reflect the availability of iron for making new red cells. The blood film shows microcytic hypochromic red cells, pencil cells and occasional target cells (Figure 1.2, Table 1.2).

Box 1.2 Investigations in iron deficiency anaemia.

• Full clinical history and physical examination
• Full blood count and blood film examination
• Haematinic assays (serum ferritin, iron studies, vitamin B12, folate)
• % hypochromic red cells and reticulocyte Hb content (if available and diagnosis is uncertain)
• Urea and electrolytes, liver function tests
• Coeliac serology
• Urinalysis
• Fibreoptic and/or CT imaging studies of the gastrointestinal tract
• Pelvic ultrasound (females, if indicated)

Figure 1.2 Blood film showing changes from iron-deficiency anaemia.

Table 1.2 Diagnosis of iron deficiency anaemia.