Changes

July 2026 — minor update. Changed wording regarding interpretation of ferritin results following feedback, so that patient context is explicit.

Update

Goals

To support primary healthcare professionals to:

• Make a diagnosis of iron deficiency anaemia.
• Investigate the cause of iron deficiency anaemia.
• Treat iron deficiency anaemia effectively.
• Refer people with iron deficiency anaemia when appropriate.

Outcome measures

Audit criteria

QOF indicators

QIPP - Options for local implementation

NICE quality standards

What is it?

• Iron deficiency occurs as a result of long-term negative iron balance. The iron deficiency spectrum ranges from iron depletion to iron deficiency anaemia.
• Iron deficiency anaemia is defined as diminished red blood cell production due to low iron stores in the body — it is the most common cause of microcytic, hypochromic anaemia, in which the two red cell indices (mean cell volume [MCV] and mean cell haemoglobin [MCH]) are reduced and the blood film shows small (microcytic) and pale (hypochromic) red cells.
• The World Health Organisation (WHO) defines anaemia as a haemoglobin (Hb) level two standard deviations below the normal for age and sex.
  • In men aged over 15 years — Hb below 130 g/L.
  • In non-pregnant women aged over 15 years — Hb below 120 g/L.
  • In children aged 12–14 years — Hb below 120 g/L.
  • In pregnant women — Hb below 110 g/L throughout pregnancy.
    • An Hb level of 110 g/L or more appears adequate in the first trimester, and a level of 105 g/L appears adequate in the second and third trimesters.
  • Postpartum — below 100 g/L.
• The British Society of Gastroenterology defines anaemia as a Hb concentration below the lower limit of normal for the relevant population, with a laboratory performing the test.
• A serum ferritin level of less than 30 micrograms/L confirms iron deficiency.

[Short, 2013; Hoffbrand, 2019; Pavord, 2020; Snook, 2021]

What causes it?

• The cause of Iron deficiency anaemia is often multifactorial, and can be broadly attributed to:
  • Dietary deficiency — this is rarely a cause on its own in adults. It takes about 8 years for a healthy adult male to develop iron deficiency anaemia due to a poor diet or malabsorption resulting in no iron intake. 
  • Malabsorption — for example, due to coeliac disease, gastrectomy, or Helicobacter pylori infection.
    • Other uncommon gastrointestinal causes include oesophagitis, schistosomiasis or hookworm, and inflammatory bowel disease.
  • Increased loss — chronic blood loss, especially from the uterus or gastrointestinal tract (GI).
    • In adult men and postmenopausal women, GI blood loss is the most common cause of iron deficiency anaemia. It can be caused by aspirin or nonsteroidal anti-inflammatory drug use, colonic carcinoma, gastric carcinoma, benign gastric ulceration, and angiodysplasia.
    • Menstruation is the most common cause of iron deficiency anaemia in premenopausal women.
    • Other gynaecological causes include haemorrhage in childbirth.
  • Increased requirement — physiological iron requirements are three times higher in pregnancy than they are in menstruating women, with increasing demand as pregnancy advances.
  • Other causes — these include blood donation, self-harm, haematuria (rare), nosebleeds (rare), and medication.

[Hoffbrand, 2019; Pavord, 2020; Snook, 2021; BMJ Best Practice, 2022]

How common is it?

• Anaemia of any cause affects around 30% of the global population.
• Iron deficiency affects around 1 billion people worldwide, and is the most common cause of anaemia.
  • It is especially prevalent in lower-income regions, such as sub-Saharan Africa, South Asia, and the Caribbean.
• Iron deficiency anaemia remains a significant problem in the developed world, and has a prevalence of 2–5% among adult men and postmenopausal women.
• In the UK, it is estimated that 3% of men and 8% of women have iron deficiency anaemia.
  • 57, 000 emergency admissions to UK hospitals each year are due to iron deficiency anaemia.
  • Iron deficiency anaemia is the reason for at least 10% of gastroenterology referrals.
• During childbearing years, there is a higher incidence of iron deficiency anaemia in women because they lose iron through menstruation and pregnancy.
  
  • The UK prevalence of iron deficiency anaemia in premenopausal women is up to 12%.
  • The UK prevalence of anaemia is estimated to be 23% in pregnant women.

[Hoffbrand, 2019; Firth, 2020; Pavord, 2020; Snook, 2021; BMJ Best Practice, 2022]

What are the complications?

• The complications of iron deficiency anaemia can include:
  • Cognitive and behavioural impairment in children — especially attention deficits. 
  • Impaired muscular performance — endurance and exercise capacity are reduced. 
  • Heart failure — high-output heart failure can occur in people with severe anaemia, especially in those with a haemoglobin level of less than 50 g/L.
  • Adverse effects on immune status and morbidity from infection (for all age groups). 
  • Visual impairment due to retinal haemorrhage (in very severe, rapid onset cases).
• Iron deficiency anaemia in pregnancy has been associated with a number of problems, including:
  • Increased morbidity for the mother and infant, and the possibility of lower birthweight.
  • Preterm delivery — increased risk of preterm delivery and perinatal mortality.
  • Maternal postpartum fatigue, altered cognition, and depressive symptoms — this in turn may affect the woman's interactions with the infant.
  • Infant iron deficiency in the first three months of life (by a variety of mechanisms).

[Badham, 2017; Hoffbrand, 2019; Pavord, 2020; Snook, 2021; BMJ Best Practice, 2022]

How should I assess someone with suspected iron deficiency anaemia?

• Diagnosis of anaemia caused by iron deficiency is made by taking a history, performing an examination, and through investigations.
• Take a detailed medical history, and ask about: 
  • Symptoms of anaemia. 
    • If the anaemia is severe, ask about specific cardiac symptoms (for example angina, palpitations, and ankle swelling).
  • Diet (to identify poor iron intake).
  • Drug history (for example the use of aspirin, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, clopidogrel, corticosteroids, and long-term proton pump inhibitors).
  • A family history of:
    • Iron deficiency anaemia (which may indicate inherited disorders of iron absorption).
    • Bleeding disorders and telangiectasia.
    • Colorectal carcinoma.
    • Haematological disorders (for example thalassaemia).
    • Gastrointestinal disorders. 
  • Resectional or bypass surgery of the GI tract including bariatric surgery.
  • A history of overt bleeding, heavy bruising, blood loss during surgery, or blood donation.
  • A history of recent illness that might suggest underlying gastrointestinal bleeding.
  • Menstrual history, pregnancy, or breastfeeding (if appropriate).
  • Travel history (increased risk of hookworm in travellers to the tropics).
  • Weight loss.
  • Exercise regime — iron deficiency anaemia is common in endurance athletes.
• Examine the person to look for signs of anaemia.
• Arrange necessary investigations.
• Consider other causes of anaemia.

What are the signs and symptoms of iron deficiency anaemia?

• Symptoms associated with iron deficiency anaemia depend on how quickly the anaemia develops.
  • People with chronic, slow blood loss may be able to tolerate very low levels of haemoglobin (for example less than 70g/L) with few symptoms.
  • Fatigue and mild dyspnoea after exertion may be the only symptoms in otherwise healthy people with slow-onset anaemia.
• Very common symptoms of anaemia include:
  • Dyspnoea.
  • Fatigue.
  • Headache.
• Common symptoms of anaemia include:
  • Cognitive dysfunction.
  • Restless leg syndrome.
• Rare symptoms of anaemia include:
  • Dysphagia (in association with oesophageal web which occurs in Patterson-Brown-Kelly or Plummer-Vinson syndromes).
  • Haemodynamic instability.
  • Syncope.
• Other symptoms include:
  • Dizziness or lightheadedness.
  • Weakness.
  • Dysgeusia.
  • Irritability.
  • Palpitations.
  • Pica (abnormal dietary cravings, for example for ice or dirt).
  • Pruritus.
  • Sore tongue.
  • Tinnitus.
  • Impairment of body temperature regulation (in pregnant women).
• Serious symptoms such as worsening of pre-existing anginal pain, ankle oedema, or dyspnoea at rest are unlikely unless the haemoglobin level is less than 70g/L, and this indicates 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, lack of concentration, and irritability.
• Common or very common signs of iron deficiency include:  
  • Pallor – this may be observed even with mild anaemia.
  • Atrophic glossitis.
  • Dry and rough skin, dry and damaged hair. 
  • Diffuse and moderate alopecia.
• Other signs of iron deficiency include: 
  • Angular cheilosis (ulceration of the corners of the mouth).
  • Nail changes, such as longitudinal ridging and koilonychia (spoon-shaped nails).
  • Worsening of pre-existing tachycardia, murmurs, cardiac enlargement, and heart failure may occur if anaemia is severe (haemoglobin less than 70g/L).
• There may be an absence of signs, even if the person has severe anaemia.

What investigations should I arrange to confirm iron deficiency anaemia?

• For people with suspected iron deficiency anaemia, arrange a full blood count (FBC).
• If results of the FBC show a low haemoglobin and low mean cell volume (MCV) check the ferritin level — check the ferritin level in all people with an MCV less than 95 femtolitres. 
  • Consider checking ferritin levels for pregnant women, but be aware that results may be less reliable in pregnancy.
• For information on how to interpret results from investigations, see the sections on interpreting a full blood count and interpreting ferritin levels.
• If iron deficiency anaemia is suspected despite serum ferritin results within an expected range, consider diagnostic trials of iron treatment. This should only be considered in premenopausal women with a history of menorrhagia, or pregnant women (if there is no suspicion of coeliac disease).
  • Note: a diagnostic trial of iron treatment should not be used for men and postmenopausal women. These people are at higher risk of occult gastrointestinal bleeding and malignancy and further investigations should be arranged. 
• For information on how to manage people with confirmed iron deficiency, see the section on confirmed deficiency.
• It is less clear in which groups of people vitamin B12 and folate levels should also be checked, and when this should be done. Consider this particularly if the person is anaemic and:
  • The anaemia is normocytic with a low or normal ferritin level.
  • There is an inadequate response to iron supplements in proven iron deficiency anaemia and no reason for this (for example poor compliance) is apparent.
  • Vitamin B12 or folate deficiency is suspected (for example due to dietary deficiency, malabsorption, or lack of folate supplementation in pregnancy).
  • The person is in an older age group (more at risk of pernicious anaemia).
• For more information on testing vitamin B12 and folate levels, see the CKS topic on Anaemia - B12 and folate deficiency.

When should I consider a diagnostic trial of iron treatment?

• If the diagnosis of iron deficiency anaemia is in doubt despite serum ferritin results, a diagnostic trial of oral iron treatment for 2-4 weeks may be considered in premenopausal women with a history of menorrhagia, or pregnant women (if there is no suspicion of coeliac disease).
  • A diagnostic trial of iron treatment should not be used for men and postmenopausal women — gastrointestinal sources of bleeding need to be excluded. 
• A trial of oral iron should be considered as the first-line diagnostic test for normocytic or microcytic anaemia in pregnant women with no haemoglobinopathy.
  • In women with known haemoglobinopathy, serum ferritin should be checked before starting a trial of iron.
  • In women with unknown haemoglobinopathy status, a trial of iron should be offered. However, haemoglobinopathy screening should be undertaken without delay in accordance with the NHS sickle cell and thalassaemia screening programme guideline, but with an awareness that iron deficiency can lower the haemoglobin A₂ percentage.
• For more information about iron treatment, see Treating iron deficiency anaemia.
• For more information about when to test to confirm a response to treatment, see Monitoring during treatment.

How should I manage people with confirmed iron deficiency?

• For people with a confirmed diagnosis of iron deficiency anaemia, ideally document the likely cause — if there is no obvious cause, appropriate further investigation is generally guided by the person's age and sex.
• For all people with iron deficiency anaemia:
  • Screen for coeliac disease using coeliac serology (presence of anti-tissue transglutaminase antibodies).
    • If positive, refer for further investigations. For more information, see the CKS topic on Coeliac disease.
  • Test the urine for blood.
  • Offer faecal immunochemical testing (FIT) to guide referral of suspected colorectal cancer in adults. For more information, see the CKS topic on Gastrointestinal tract (lower) cancers - recognition and referral.
• Consider stool examination to detect parasites, if appropriate from the person's travel history.
• It is usually unnecessary to further investigate the following groups of people prior to treatment:
  • Otherwise healthy young people in whom history clearly suggests a cause — for example, regular blood donors.
  • Menstruating young women with no history of gastrointestinal symptoms or family history of colorectal cancer.
  • 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). 
    • There is no response to iron supplementation.
  • 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.
  • People who refuse further investigations.
• Refer people where appropriate, or treat people depending on the underlying cause.  
  •  For information on appropriate investigations for women with heavy menstrual bleeding, see the CKS topic on Menorrhagia.

What else might it be?

• The differential diagnosis of microcytic anaemia includes:
  • Thalassaemia — for people with thalassaemia trait (alpha or beta), the mean cell volume (MCV) and mean cell haemoglobin (MCH) concentration are all reduced and are very low for the degree of anaemia.
  • Sideroblastic anaemias (very rare) — alcoholism can be a cause of reversible sideroblastic anaemia. Hepatosplenomegaly is found in a third to a half of people with sideroblastic anaemia and is not present in iron deficiency anaemia.
  • Anaemia of chronic disease — on analysis of the full blood count (FBC), in 80% of cases, anaemia of chronic disease is normocytic and normochromic. However, in 20% of cases, it can present as microcytic, hypochromic anaemia like iron deficiency anaemia.
  • Lead poisoning (rare in adults) — people may have a history of risk factors, such as occupational exposures (for example, exposure to lead paint).
• Thalassaemia and sideroblastic anaemia are both associated with an accumulation of iron, so tests will show an increase in serum iron and ferritin, and a low total iron-binding capacity.

Scenario: Management of iron deficiency anaemia

From age 12 years onwards.

Iron content in different iron salts

Table 1. Iron content of oral iron preparations

Adverse effects

• Adverse effects of iron supplements include:
  • Constipation.
  • Diarrhoea.
  • Epigastric pain.
  • Faecal impaction.
  • Gastrointestinal irritation.
  • Nausea.
• Adverse effects are dose-related and are directly related to the amount of iron absorbed (although the relationship between constipation or diarrhoea is less clear than for nausea and epigastric pain).
  • The incidence of adverse effects is no greater with ferrous sulfate than with other iron salts.
• Adverse effects of oral iron supplements are a common cause of non-compliance with treatment — 10–20% of people are thought to discontinue iron supplements because of adverse effects.  
• If adverse effects are troublesome, the following may help to minimize them:
  • Taking the iron supplement with or after food — iron supplements are better tolerated when taken with or after food. However, this may decrease iron absorption by 40–66%.
  • Reducing the dose frequency to alternate days — there is evidence to suggest that alternate day dosing may optimise iron absorption.

[Short, 2013; Lopez, 2016; BMJ Best Practice, 2022; BNF, 2023]

Drug interactions

• Oral iron supplements reduce the absorption of some drugs if taken concurrently, including: 
  • Tetracyclines.
  • Quinolones.
  • Bisphosphonates.
  • Zinc.
• The absorption of oral iron is reduced if taken concurrently with:
  • Zinc or magnesium salts (for example in antacids).
  • Calcium (for example in milk and dairy products).
  • Tannins (for example in tea, coffee, and cocoa).
  • Phytates (present in cereal grains, legumes, nuts, and seeds).
• Interactions may occur with the following drugs if taken concurrently with oral iron supplements: 
  • Methyldopa — the antihypertensive effect can be reduced.
  • Levodopa — the bioavailability may be reduced.
  • Levothyroxine — the effects of levothyroxine may be reduced.
  • Penicillamine — the absorption may be reduced by as much as two-thirds.

[ABPI, 2021; BNF, 2023; Preston, 2019]

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of anaemia - iron deficiency.

Search dates

April 2018 - April 2023

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• exp Anemia/, anemia.tw., anaemia.tw., exp Anemia, Iron-Deficiency/, iron deficiency.tw., iron-deficiency, deficien$.tw., exp Iron/

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.