CHAPTER 1
Iron-Deficiency Anaemia

Drew Provan1 and Catherine Booth2

1 Department of Haematology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

2 Barts and the London NHS Trust, 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.

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 (Box 1.1).

Box 1.1 Risk factors for development of iron deficiency.

• Age: infants (especially if history of prematurity); adolescents; premenopausal women; old age
• Gender: increased risk in women
• Reproduction: pregnancy, breast feeding
• Travel/country of origin: parasites (e.g. hookworm, schistosoma)
• Gastrointestinal pathology: appetite or weight changes; changes in bowel habit; bleeding from rectum/melaena; gastric or bowel surgery
• Drug history: especially aspirin and non-steroidal anti-inflammatories
• Social history: diet, especially vegetarianism, age of weaning of infants

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 (Table 1.1, Box 1.2).

Table 1.1 Daily dietary iron requirements.

Box 1.2 Causes of iron-deficiency anaemia.

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

Reproductive system

• Menorrhagia

Gastrointestinal tract

Bleeding

• Oesophagitis
• Oesophageal varices
• Hiatus hernia (ulcerated)
• Peptic ulcer
• Inflammatory bowel disease
• Haemorrhoids (rarely)
• Carcinoma: stomach, colorectal
• Angiodysplasia
• Hereditary haemorrhagic telangiectasia (rare)
• Hookworm infection - commonest cause of iron deficiency worldwide

Malabsorption

• Coeliac disease
• Atrophic gastritis (also may result from iron deficiency)
• Infection: Helicobacter pylori, tropical sprue
• Post-surgical: gastric bypass, small bowel resection

Renal tract

• Haematuria - Schistosoma haematobium infection
• Intravascular haemolysis with renal haemosiderin excretion

Physiological (increased demand)

• Growth spurts (especially in premature infants)
• Pregnancy, lactation

Dietary

• Vegans
• Elderly
• Infants under 12 months fed predominantly on cow's milk

Other

• Iatrogenic: multiple blood sampling (especially premature infants)
• Patients with chronic renal failure undergoing haemodialysis and receiving erythropoietin

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 (e.g. <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, resolving promptly with iron replacement. In children, chronic iron-deficiency anaemia can lead to impaired psychomotor and cognitive development.

On examination, several skin, nail and other epithelial changes may be seen in chronic iron deficiency. Atrophy of the skin occurs in about a third of patients, and (rarely nowadays) nail changes such as koilonychia (spoon-shaped nails) may result in brittle, flattened nails (Figure 1.1). 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.

Figure 1.1 Nail changes in iron-deficiency anaemia (koilonychia).

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 (e.g. as in 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 1.2).

Figure 1.2 Diagnosis and investigation of iron-deficiency anaemia.

Diet alone is seldom the sole cause for 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.

Laboratory investigations

A full blood count and film should be assessed (Box 1.3). 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 (MCHC). Some modern analysers will determine the percentage of hypochromic red cells, which may be high before the anaemia develops (it is worth noting that a reduction in haemoglobin concentration is a late feature of iron deficiency - the first change being an increase in the red cell distribution width). There may be a reactive thrombocytosis. The blood film shows microcytic hypochromic red cells, pencil cells and occasional target cells (Table 1.2, Figure 1.3).

Table 1.2 Diagnosis of iron-deficiency anaemia (normal values in parentheses).