Iron-Deficiency Anaemia (IDA)

Please note that there are separate articles entitled 'Anaemia in Childhood' and 'Anaemia in Pregnancy' that cover iron deficiency anaemia in these patient groups.

Iron deficiency anaemia (IDA) occurs when the body is iron deficient to the extent that red blood cell production is reduced.^1,2 A state of non-anaemic iron deficiency usually precedes actual anaemia. Iron deficiency is the most common cause of anaemia worldwide.

The World Health Organisation defines anaemia as:¹

• Hb <13 g/dL in men over 15 years old
• Hb <12 g/dL in non-pregnant women over 15 years old
• Hb <12 g/dL in children aged 12-14 years

Failure to investigate IDA properly by practitioners in primary care can cause significant delay in final diagnosis with associated morbidity.³ This article is based on the Clinical Knowledge Summary Guidance on iron deficiency anaemia.⁴

• In the developed world, 2-5% of adult men and post-menopausal women have iron deficiency anaemia.⁵
• 4-13% of referrals to gastroenterologists are because of iron deficiency anaemia.⁵
• Pre-menopausal women have a higher incidence of iron deficiency anaemia because of heavy menstrual blood losses and pregnancy.²

Causes of iron deficiency may be classified as those due to:

Excessive blood loss

• Blood loss from the gastrointestinal tract is the commonest cause of iron deficiency anaemia in adult men and postmenopausal women.⁴
• Blood loss due to menorrhagia is the commonest cause of iron deficiency in premenopausal women.
• In other countries, infestation of the gut may cause IDA, especially with hookworm and schistosomiasis.
• Common causes of blood loss include:
  • Non steroidal anti-inflammatory drug (NSAID) use
  • Colonic carcinoma
  • Gastric carcinoma
  • Gastric or duodenal ulceration
  • Angiodysplasia
  • Heavy menstruation
• Other causes include:
  • Other gastrointestinal tract malignancies
  • Bleeding oesophageal varices
  • Inflammatory bowel disease
  • Haemorrhoids
  • Oesophagitis and gastro-oesophageal reflux disease
  • Post-partum haemorrhage
  • Recurrent epistaxis
  • Malignancy of the renal tract
  • After major surgery of major trauma if replacement has been inadequate
  • After blood donation

Dietary inadequacy

• Dietary iron deficiency is fairly uncommon.
• Meat tends to be more rich in iron than vegetables and so vegetarians are at greater risk. However, green vegetables are a good source of iron and a proper vegetarian diet should not lead to deficiency.
• Growing children and elderly people with iron-poor diets may become deficient.

Failure of iron absorption

• Not only does the diet have to contain adequate amounts of iron but the iron has to be in a form that can be absorbed.
• Iron can be absorbed in the ferrous state much more readily than in the ferric state.
• Factors affecting iron absorption:
  • Some drugs can bind to iron and prevent absorption. Tetracyclines and quinolones chelate with iron so that neither the antibiotic nor the iron is absorbed.
  • Antacids and proton pump inhibitors may also impair absorption by raising gastric pH.⁴
  • Phytate (found in wholegrain cereals, nuts, seeds and legumes), polyphenols (found in tea and coffee) and calcium (in dairy products) impair iron absorption. Iron absorption can be increased in a diet rich in fish, red and white meat.^6,7
  • Vitamin C may enhance iron absorption. Patients can be encouraged to drink a glass of orange juice with their iron tablets.
  • Malabsorption conditions such as coeliac disease (usually accompanied by folate deficiency).
  • May occur after partial or total gastrectomy, more commonly with increased number of post-operative years.⁸
  • Helicobacter pylori colonisation appears to impair iron uptake and increase iron loss.

Excessive requirements for iron

• Times of high demand for iron should be met by greater absorption from the diet.
• If the diet is not adequate, an intake that would otherwise be sufficient becomes inadequate. For example in:
  • Times of rapid growth in children
  • Pregnancy, especially with twins
  • Exfoliative skin disease

Iron deficiency anaemia is often an incidental finding rather than a presenting feature. Chronic, slow blood loss can lead to compensation by the body and little in the way of symptoms. If symptoms occur, they can include:

• Fatigue
• Shortness of breath on exertion
• Palpitations
• Sore tongue and taste disturbance
• Changes in the hair/hair loss
• Pruritis
• Headache
• Tinnitus
• Angina can occur if there is pre-existing coronary heart disease
• Very rarely, there may be dysphagia due to an oesophageal web with chronic iron deficiency. This is the Paterson-Brown-Kelly or Plummer-Vinson Syndrome and there is an association with oesophageal carcinoma.

Symptoms of severe anaemia (usually not occurring until Hb is <7 g/dL) include: shortness of breath at rest, angina and ankle swelling. These symptoms may occur at higher Hb levels if there is co-existing cardiorespiratory disease).⁴

To look for potential causes, cover the following points:

• Current/recent diet - could account for poor iron intake
• Drug history - NSAIDs, SSRIs, clopidogrel, corticosteroids could be a potential cause
• Any overt bleeding seen by patient - e.g. nosebleeds, rectal bleeding etc.
• History of recent blood donation
• Menstrual history in women
• History of recent illness - could suggest gastrointestinal bleeding, e.g. weight loss, change in bowel habit, dyspepsia
• History of previous gastrointestinal disease or surgery
• Travel history - e.g. hookworm infestation is possible if recent travel to the tropics
• Family history - including inherited haematological disorders such as thalassaemia; bleeding disorders and telangiectasia; iron deficiency anaemia (may indicate potential inherited disorder of iron absorption)

• Examine the abdomen for abdominal masses, organomegaly, lymphadenopathy and any other features of intra-abdominal disease.
• Perform a rectal examination to look for signs of bleeding, melaena and masses.
• If menorrhagia is thought to be the cause: perform a vaginal/bimanual examination, examine the cervix and perform a cervical smear and swabs as appropriate (please refer to article on menorrhagia for further details).

Signs

• Pallor (best seen in the mucosa of tongue and mouth, especially in people with dark skin)
• Koilonychia (spoon shaped nails with longitudinal ridging)
• Angular cheilitis (ulceration at the corners of the mouth)
• Atrophic glossitis
• In marked anaemia there may be tachycardia, a flow murmur, cardiac enlargement, ankle oedema and heart failure.

• Stigmata of chronic liver disease, perhaps cirrhosis
• Multiple telangiectasia may be a feature of hereditary haemorrhagic telangiectasia, also known as Osler-Weber-Rendu Syndrome
• Pigmentation of the lips and oral mucosa may suggest Peutz-Jeghers syndrome

• Full blood count: shows a hypochromic microcytic anaemia (although there may be a mixed picture with coexistent B12 or folate deficiency).
  • Hypochromia means that there is as a low mean corpuscular haemoglobin (MCH).
  • Microcytosis means that there is as a low mean corpuscular volume (MCV).
  • Remember that a haemoglobinopathy will also cause a hypochromic microcytic anaemia.
• Serum ferritin: should be measured to confirm iron deficiency (except during pregnancy).
  • This correlates with total body iron stores.
  • However, ferritin levels can be raised if infection or inflammation is present, even if iron stores are low.¹
  • A ferritin level < 15 mcg/L confirms iron deficiency.⁵
  • If there is coexisting chronic inflammatory disease, the clinician should consider seeking specialist advice about other measures of iron status.
• Blood film: anisocytosis (variation in size between red blood cells) and poikilocytosis (abnormally shaped red blood cells) can be seen.

Other causes of microcytic anaemia including:

• Thalassaemia
• Sideroblastic anaemia
• Anaemia of chronic disease
• Lead poisoning

• Urinalysis for blood (approximately 1% of patients with iron deficiency anaemia have a renal tract malignancy)
• Screening for coeliac disease (serology looking for anti-endomysial antibody or tissue transglutaminase antibody)
• Referral for upper and lower gastrointestinal investigations
• Stool examination looking for parasites if recent travel to endemic area

• If someone has profound anaemia and signs of acute heart failure, they should be admitted urgently to hospital.
• People of any age with dyspepsia and iron deficiency anaemia should be referred for endoscopy, or to a specialist in upper gastrointestinal cancer, within 2 weeks.
• Men of any age with unexplained iron deficiency anaemia and a haemoglobin of 11 g/dL or below, should be referred within 2 weeks to a gastroenterologist.
• Women who are not menstruating with unexplained iron deficiency anaemia and a haemoglobin of 10 g/dL or below should be referred within 2 weeks to a gastroenterologist.

• Someone is unable to tolerate, or is not responding to, oral iron treatment.
• If someone who has initially responded to oral iron treatment develops anaemia again with no obvious cause.
• If a women with menorrhagia and iron deficiency anaemia has failed to respond to treatment she should be referred to a gynaecologist.

• Treatment for the iron deficiency should be started before the results of the investigations.
• Start ferrous sulphate 200 mg two to three time per day.
• Explain common side effects and how to reduce them (see below).
• Advise about storage of iron supplements out of the reach of children.
• Ferrous fumarate or ferrous gluconate are alternatives if ferrous sulphate isn't tolerated.
• When the underlying cause is known, this should be managed appropriately.
• Iron-rich foods include dark green vegetables, meat, apricots, prunes, raisins and iron-fortified bread.
• Consider referral to a dietician if diet is thought to be the cause.

Common side effects usually reduce with time and include:

• Constipation
• Black stools
• Diarrhoea
• Heartburn
• Nausea
• Abdominal/epigastric pain

Full blood count should be checked 2-4 weeks after treatment has started.

If there is response to treatment

• Check full blood count again in 2-4 months to ensure haemoglobin levels have returned to normal.
• Once haemoglobin levels are normal, continue treatment for 3 months.
• Re-check full blood count every 3 months for 1 year.
• Re-check again after a further year.
• If haemoglobin or red cell indices drop below normal, give additional iron.

If there is inadequate response to treatment

• Assess compliance; is the iron supplement tolerated?
• If there are problems with compliance:
  • Consider prescribing a laxative if constipation.
  • Advise patient to take iron with or after meals.
  • Reassure the patient that black stools are normal and harmless.
  • Reduce the frequency of the iron supplement to one or two times per day.
  • Try a different formulation with a lower content of elemental iron, e.g. ferrous gluconate.
• If oral supplements are still not tolerated, ask for specialist advice. If the patient is unable to tolerate oral iron or there is malabsorption, parenteral iron can be given. This is not recommended in primary care.⁴ Transfusion is occasionally necessary.
• If there is an increase of less than 2 g/dL in the haemoglobin level after 2-4 weeks, refer for specialist assessment and advice.