Iron Deficiency Anaemia

 

Iron deficiency occurs when the body's iron demand is not met by iron absorption from the diet.  Iron deficiency anaemia occurs in the more severe stages of iron deficiency when the body is iron deficient to the degree that red blood cell production is reduced.  Iron deficiency is the most common deficiency state in the world, affecting over two billion people worldwide.  Iron deficiency anaemia remains a significant problem in the developed world and has a prevalence of 2–5% among adult men and postmenopausal women. It is the reason for 4–13% of referrals to gastroenterologists

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Definitions

The World Health Organization defines anaemia as:

  1. In men over 15 years of age: Hb < 13 g/100 mL
  2. In non-pregnant women over 15 years of age: Hb < 12 g/100 mL
  3. In children of 12–14 years of age: Hb < 12 g/100 mL
  4. In pregnant women: Hb < 11 g/100 mL throughout pregnancy

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Causes

Common causes include:

  1. Gastrointestinal causes  blood loss from the gastrointestinal tract is the most common cause of iron deficiency anaemia in adult men and postmenopausal women, and can be caused by aspirin or nonsteroidal anti-inflammatory drug use, colonic carcinomagastric carcinoma, benign gastric ulceration, or angiodysplasia
  2. Gynaecological causes:
    1. Menstruation — the most common cause of iron deficiency anaemia in premenopausal women (20–30% of cases)
    2. Pregnancy — physiological iron requirements are three times higher in pregnancy than they are in menstruating women, with increasing demand as pregnancy advances
  3. Malabsorption, for example due to Coeliac disease, gastrectomy, and Helicobacter pylori infection
  4. Other causes, such as blood donation

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Uncommon causes include:

  1. Gastrointestinal causes, for example oesophagitis, schistosomiasis or hookworm, or inflammatory bowel disease
  2. Gynaecological causes, for example haemorrhage in childbirth
  3. Malabsorption, for example due to gut resection (rare) or bacterial overgrowth (rare)
  4. Other causes, such as haematuria (rare), nosebleeds (rare), and inadequate dietary intake (for example in elderly people or vegans)

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Signs and symptoms

NOTE Symptoms associated with iron deficiency anaemia will depend on how quickly the anaemia develops.  People with chronic, slow blood loss may be able to tolerate very low levels of haemoglobin with few symptoms

Common symptoms include:

  • fatigue
  • dyspnoea
  • palpitations

Less common symptoms include:

  • Headache
  • Tinnitus
  • Taste disturbance
  • Pruritus
  • Pica (abnormal dietary cravings, for example for ice or clay)
  • Sore tongue
  • Dysphagia (in association with oesophageal web which occurs in Patterson-Brown-Kelly or Plummer-Vinson syndromes)
  • Impairment of body temperature regulation (in pregnant women)

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NOTE:

  • Serious symptoms such as angina, marked ankle oedema, or dyspnoea at rest are unlikely at haemoglobin concentrations of more than 7 g/100 mL unless there is additional heart or lung pathology. Angina may occur if there is pre-existing coronary artery disease
  • Symptoms of iron deficiency may occur without anaemia. These symptoms include fatigue, hair loss, lack of concentration, and irritability

NOTE There may be no signs, even if the person has severe anaemia

Pallor may be observed even with mild anaemia

Less commonly, the following signs may be observed:

  • Atrophic glossitis
  • Angular cheilosis (ulceration of the corners of the mouth)
  • Nail changes, such as longitudinal ridging and koilonychia (spoon-shaped nails)
  • Tachycardia, murmurs, cardiac enlargement, and heart failure may occur if anaemia is severe (haemoglobin less than 8 g/100 mL)

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Exclude Red Flag Symptoms

Refer urgently (2 week wait pathway) if the following is seen:

  • Unexplained iron deficiency anaemia with:
- Hb < 11g/dl in men
- Hb < 10g/dl in non-menstruating women

Ensure that anaemia is due to iron deficiency before referring to gastroenterology

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Investigations

Investigations:

  • FBC
  • ferritin
  • CRP
  • B12 Folate
  • Coeliac Screen (in premenopausal women malignancy is extremely uncommon whereas coeliac disease is present in up to 4%)
  • urinalysis (1% of IDA patients will have a renal tract malignancy and thus heamaturia needs further investigation if found)

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Interpreting results:

  • Red cell indices, reduced MCH (hypochromia) and reduced MCV (microcytosis) provide a sensitive indication of iron deficiency in the absence of chronic disease or haemoglobinopathy
  • Other markers of iron deficiency anaemia include low transferrin saturation, low iron and raised total binding capacity
  • Vitamin B12 and folate deficiency should be excluded
  • Haemogobin electrophoresis is recommended to exclude a haemoglobinopathy in patients of appropriate ethnic background to prevent unnecessary GI investigation
  • Ferritin is the most powerful test for iron deficiency in the absence of inflammation

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Management

Management steps

  1. Assess the person to determine the cause and severity of anaemia
  2. Refer for further investigation to the appropriate speciality (for example gastroenterology, surgery, or gynaecology)
  3. Treat adults with iron deficiency anaemia (including pregnant women):
    1. Treat the underlying cause, if appropriate to do so in primary care
    2. Treat iron deficiency anaemia with ferrous sulphate first-line and advise about diet
  4. Monitor as appropriate

Further details for each section are shown below

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Assessment for underlying cause

Assess the person to determine the cause and severity of anaemia, through taking the history, examination and appropriate investigations

Ask about:

  • Diet (to identify poor iron intake)
  • Drug history (for example the use of aspirin, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, clopidogrel, or corticosteroids)
  • History of overt bleeding or blood donation
  • Menstrual history (if appropriate)
  • History of recent illness which might suggest underlying gastrointestinal bleeding
  • Gastrointestinal symptoms (including altered bowel habit)
  • Weight loss
  • Travel history (increased risk of hookworm in travellers to the tropics)
  • Family history of:
    • Iron deficiency anaemia (which may indicate inherited disorders of iron absorption)
    • Haematological disorders (for example thalassaemia)
    • Bleeding disorders and telangiectasia
  • If the anaemia is severe, ask about specific cardiac symptoms (for example angina, palpitations, and ankle swelling)

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Examine:

  • The abdomen for abdominal masses, organomegaly, lymphadenopathy, and other features of intra-abdominal disease
  • If there is a history of rectal bleeding and/or tenesmus, perform a rectal examination
  • Examine the cardiovascular system and chest for signs of heart failure
  • If heavy menstrual bleeding is thought to be the cause of iron deficiency anaemia

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Investigations

It is usually unnecessary to further investigate the following groups of people prior to treatment:

  1. Otherwise healthy young people in whom the history clearly suggests a cause (for example regular blood donors)
  2. Menstruating young women with no history of gastrointestinal symptoms or family history of colorectal cancer
  3. Pregnant women — investigations (to determine an underlying cause or the presence of complications) are not usually needed if anaemia develops during pregnancy unless the anaemia is severe, the history and examination suggest an alternative cause of iron deficiency (for example inflammatory bowel disease), or there is no response to iron supplementation
  4. People who are terminally ill or unable to undergo invasive investigations — the appropriateness of investigating people with severe comorbidity (or, in some circumstances, advanced age), especially if management would not be influenced by the results, should be discussed with the person and their family and carers
  5. People who refuse further investigations

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For other groups of people with iron deficiency anaemia:

  1. Test the urine for blood
  2. Refer for upper and lower gastrointestinal (GI) investigations
  3. Consider stool examination to detect parasites, if appropriate from the person's travel history
  4. If there is a poor response to empirical iron treatment, or recurrence of anaemia without an obvious cause, seek specialist advice regarding further assessment and investigation
  5. If the person has already had normal upper and lower gastrointestinal investigations for iron deficiency anaemia and the anaemia persists or recurs, consider testing for Helicobacter pylori, and eradicate if present

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Referral

For people of any age who present with:

  • Iron deficiency anaemia with dyspepsia — refer urgently (within 2 weeks) for endoscopy
  • Iron deficiency anaemia without dyspepsia — recognize the possibility of gastrointestinal cancer and consider urgent referral for further investigations
    • In all cases, both upper and lower gastrointestinal investigations are recommended, unless the upper gastrointestinal endoscopy detects gastric cancer or coeliac disease (in which case lower gastrointestinal investigations are not necessary)

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For men of any age with:

  • unexplained iron deficiency anaemia and a haemoglobin level of 11 g/100 mL or below — refer urgently (within 2 weeks) for upper and lower gastrointestinal investigations

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For women who are not menstruating, with:

  • unexplained iron deficiency anaemia and a haemoglobin level of 10 g/100 mL or below — refer urgently (within 2 weeks) for upper and lower gastrointestinal investigations

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NOTE:  People with unexplained iron deficiency anaemia who do not fulfil these criteria for urgent referral will still require referral for upper and lower gastrointestinal investigation. The urgency of this will require clinical judgement, based on the haemoglobin level and clinical findings

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Refer / seek specialist advice:

  1. If coeliac serology is positive — refer to gastroenterology
  2. If the person has profound anaemia with signs of heart failure — admit to hospital
  3. If a woman with menorrhagia has iron deficiency anaemia that has failed to respond to treatment — refer to a gynaecologist (urgency of referral should reflect clinical judgement)
  4. If a person is unable to tolerate, or is not responding to, oral iron treatment — seek specialist advice
  5. If a person who has initially responded to iron treatment develops anaemia again without an obvious underlying cause — seek specialist advice regarding further assessment and investigation

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If 2 week wait referral not indicated:

  1. All postmenopausal women and all men with iron deficiency anaemia should be considered for upper and lower GI investigations
  2. Premenopausal women should be screened for coeliac disease but only offered other GI investigations if >50, GI symptoms or significant family history of GI cancer
  3. Frail elderly patients or those with significant co-morbidities need to be considered on a case by case basis. Risks and benefits of bowel prep and procedures need to be considered and the ability to mobilize on a table for endoscopic examinations. CT colography (this does need bowel prep) or unprepared CT may be more appropriate than invasive colonoscopy
  4. Patients with treated coeliac disease who develop iron deficiency anaemia should have further GI investigation if >50, have GI symptoms or have significant history of GI cancer

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Treatment

Discuss with the patient:

  1. Dietary iron intake
  2. NSAID use (if using advise to stop unless very good reason not to)
  3. Family history of blood disorders e.g. thalassaemia, bleeding disorders of IDA (may indicate inherited problem with iron absorption or need of Hb electrophoresis)
  4. History of blood donation or other obvious blood loss (recent surgery?)
  5. Significant family history of colorectal cancer (one affected 1st degree relative <50 years old or 2 affected 1st degree relatives

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Treatment options:

  1. Treat with oral ferrous sulphate 200 mg tablets two or three times a day
    1. If ferrous sulphate is not tolerated, consider oral ferrous fumarate tablets or ferrous gluconate tablets
    2. Do not wait for investigations to be carried out before prescribing iron supplements
  2. If poor response to iron consider referral for repeat OGD or video capsule endoscopy of small bowel (this may reveal an alternative bleeding cause such as a gastro intestinal stromal tumour (GIST), angiodysplasia or Crohn’s disease)
  3. If dietary deficiency of iron is thought to be a contributory cause of iron deficiency anaemia, advise the person to maintain an adequate balanced intake of iron-rich foods (for example dark green vegetables, iron-fortified bread, meat, apricots, prunes, and raisins) and consider referral to a dietitian

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‘Feraccru use in Iron Deficiency Anaemia in IBD’ (EKPG) Sept 2018

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Monitoring drug treatment

  1. Recheck haemoglobin levels (FBC) after 2–4 weeks to assess the person's response to iron treatment. The haemoglobin concentration should rise by about 2 g/100 mL over 3–4 weeks
    1. If there is a response, check the full blood count at 2–4 months to ensure that the haemoglobin level has returned to normal
  2. Once haemoglobin concentration and red cell indices are normal:
    1. Continue iron treatment for 3 months to aid replenishment of iron stores, and then stop
    2. Then monitor the person's full blood count every 3 months for 1 year
    3. Recheck after a further year, and again if symptoms of anaemia develop subsequently
    4. If haemoglobin or red cell indices drop below normal, give additional iron
  3. Consider an ongoing prophylactic dose in people who are at particular risk of iron deficiency anaemia
  4. If there is a lack of response:
    1. Assess compliance and whether the iron treatment is tolerated
    2. If an oral iron supplement (usually ferrous sulphate) is not tolerated, address adverse effects by:
      1. Offering a laxative to people with constipation
      2. Offering reassurance to people who have black stools
      3. Recommending the person takes iron with or after meals
      4. Reducing the dose frequency of the iron supplement (for example one or two tablets daily)
      5. Giving a different iron formulation or salt with a lower content of elemental iron (for example ferrous gluconate)
    3. If the person is still unable to tolerate oral iron supplements, seek specialist advice
      1. People should undergo specialist assessment if there is a lack of response (that is, an increase of less than 2 g/100 mL in the haemoglobin level) after 2–4 weeks

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Blood tests / Phlebotomy

If your practice does not have a practice nurse who is trained to take bloods, you can refer a patient to the Pathology Department at East Kent Hospitals for a blood test (find details here)

Alternatively, Buckland Hospital (Dover) and the Royal Victoria Hospital (Folkestone) both operate a walk-in service where no appointment is necessary, except for if the patient requires a Glucose Tolerance Test (GTT).  In the event that a GTT is required, please call 01304 222552 (for Buckland) and 01303 854484 (for Royal Victoria) to arrange a suitable appointment

Please ensure that the patient remembers to take with them their blood test form to the walk-in centres

Advice and Guidance is being made available for all specialties, and is being provided by consultant specialists at East Kent Hospitals.  To make a request or to check to if a query has been answered, you will need to log in via the electronic Referral System (eRS)

Click here for the "how to access" e-Referral Advice and Guidance Manual for instructions on how to make a request and check responses

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