Haematology & Oncology

Iron-Deficiency Anaemia

Iron-deficiency anaemia reflects depleted iron available for haemoglobin production; replace the iron, but always investigate the pattern of loss, demand or malabsorption that caused it.

Definition

Iron-deficiency anaemia is anaemia caused by insufficient iron for erythropoiesis. It commonly produces iron-restricted, microcytic and hypochromic red cells, but the diagnostic priority is to establish the cause of iron depletion.

Epidemiology

Common causes include menstrual and gastrointestinal blood loss, pregnancy or growth-related demand, low intake and impaired absorption. Risk of significant gastrointestinal pathology varies with age, sex, haemoglobin, MCV, symptoms and comorbidity.

Pathophysiology

Iron stores are depleted before iron-restricted erythropoiesis reduces haemoglobin production. Later red cells become microcytic and hypochromic. Chronic loss, increased demand and reduced absorption can act alone or together; inflammation can produce functional iron restriction and a falsely reassuring ferritin.

First principles

Iron stores fall before haemoglobin production fails

Iron depletion progresses from reduced stores to iron-restricted erythropoiesis and then anaemia. Ferritin is the most useful marker of stores when there is no inflammation, but inflammation can make ferritin look falsely reassuring; interpret it with transferrin saturation and the clinical context.¹

The cause is loss, increased demand or reduced absorption

Chronic menstrual or gastrointestinal blood loss, pregnancy or growth, poor intake, coeliac disease, gastric or small-bowel disease and previous gastrointestinal surgery all fit one of these mechanisms. A good history is therefore part of the diagnostic test: ask about bleeding, diet, pregnancy, gastrointestinal symptoms, medication, surgery and family history.^1,2,3

Microcytosis is a clue, not a diagnosis

Iron restriction commonly produces low MCV and MCH, but thalassaemia, inflammation, sideroblastic disease and other conditions can also be microcytic. Confirm iron deficiency with iron studies before attributing every microcytic anaemia to iron lack or starting a prolonged replacement pathway.¹

Unexplained adult iron deficiency needs a source-finding pathway

Men and postmenopausal women do not have an expected menstrual explanation, so occult gastrointestinal or urinary blood loss and malignancy must be considered. Current NICE NG12 recommends quantitative FIT to guide suspected colorectal-cancer referral in adults with iron-deficiency anaemia; BSG specialist guidance generally recommends gastroscopy and colonoscopy as first-line GI investigations in men and postmenopausal women. A low or missing FIT does not overrule strong clinical concern.^4,1

The response to iron is both treatment and a diagnostic signal

A prompt haemoglobin response supports absolute iron deficiency, but failure to respond should trigger a structured review of adherence, ongoing blood loss, malabsorption, inflammation, renal disease, haemolysis, marrow disease and concurrent B12 or folate deficiency. Restoring haemoglobin is not the same as correcting the cause.^1,5

Presentation

Fatigue, reduced exercise tolerance, breathlessness, pallor, pica or epithelial changes may reflect iron-deficiency anaemia; the diagnostic priority is to confirm iron depletion and identify the source.^1,4,6

Cardinal features

Fatigue, lethargy, reduced concentration or reduced exercise tolerance
Exertional breathlessness, palpitations or headache
Pallor, koilonychia, angular stomatitis or glossitis
Pica, especially craving ice or other non-food substances
Symptoms or signs of menstrual, gastrointestinal or urinary blood loss
Abdominal symptoms, weight loss, altered bowel habit or dysphagia suggesting an underlying gastrointestinal disorder

Red flags

Chest pain, syncope, breathlessness at rest, heart failure, haemodynamic instability or rapidly falling haemoglobin
Melaena, rectal bleeding, haematemesis or other ongoing overt blood loss
Iron-deficiency anaemia in a man or postmenopausal woman without an adequate explanation
Weight loss, abdominal mass, change in bowel habit, dysphagia or persistent upper gastrointestinal symptoms
Failure to respond to oral iron, recurrent anaemia after correction or intolerance preventing treatment
Older age, frailty, anticoagulant use, chronic kidney disease or inflammatory disease complicating assessment

Investigations

FBC, indices, reticulocytes and blood film

Confirm anaemia against the laboratory reference range and assess MCV, MCH, red-cell count, RDW, platelets and white cells. A blood film may support iron restriction and identify features suggesting thalassaemia, haemolysis, marrow disease or another process.

Expected finding: Low haemoglobin with low MCV and MCH is common, but early iron deficiency can be normocytic and microcytosis is not specific.

Ferritin with transferrin saturation and inflammatory context

Ferritin is the most useful marker of iron stores in the absence of inflammation. If ferritin is normal or raised despite a compatible picture, check transferrin saturation and interpret the result with CRP or other evidence of inflammation; a response to iron can support the diagnosis when studies are equivocal.

Expected finding: Low ferritin and low transferrin saturation support absolute iron deficiency; ferritin may be falsely normal in inflammation.

Directed history, examination and additional blood tests

Ask about menstrual bleeding, pregnancy, diet, blood donation, gastrointestinal or urinary symptoms, anticoagulants and NSAIDs, previous gastrointestinal or bariatric surgery, family history and inflammatory disease. Add renal, liver, thyroid, B12, folate, haemolysis or haemoglobinopathy testing when the presentation suggests an alternative or mixed cause.

Expected finding: The history may identify a plausible source, but an apparent explanation should not stop appropriate investigation when the patient is in a higher-risk group or the response is inadequate.

^1,3

Urinalysis or urine microscopy

Urinary blood loss and renal tract disease are alternative or additional causes of iron deficiency. Urinalysis is part of the initial assessment, but a negative result does not fully exclude renal pathology when anaemia is recurrent or unexplained.

Expected finding: Microscopic haematuria may redirect assessment to the renal or urological pathway; a normal result does not remove the need for gastrointestinal assessment when indicated.

Coeliac serology while eating gluten

NICE recommends serological testing for unexplained iron deficiency. In adults, request total IgA and IgA tissue-transglutaminase as first choice, with an IgA-deficiency pathway. Testing is only reliable while the person is consuming gluten; do not start a gluten-free diet before specialist confirmation.

Expected finding: Positive serology requires gastrointestinal specialist assessment; negative serology does not exclude coeliac disease if clinical suspicion remains high.

^2,1

Quantitative FIT and current colorectal referral pathway

NICE NG12 recommends offering quantitative FIT to adults with iron-deficiency anaemia to guide suspected colorectal-cancer referral. A result at or above the current NICE cut-off meets the suspected-cancer referral threshold; if the sample is not returned or the result is below the cut-off, safety-netting and clinical judgement remain essential.

Expected finding: A positive FIT increases the urgency of colorectal referral, but a negative, low or missing FIT does not justify ignoring persistent symptoms, anaemia, an abdominal mass or strong clinical concern.

^4,1

Bidirectional gastrointestinal investigation when indicated

BSG guidance generally recommends gastroscopy and colonoscopy as first-line GI investigations for newly diagnosed iron-deficiency anaemia in men and postmenopausal women, with CT colonography as an alternative when colonoscopy is unsuitable. In younger menstruating women, investigation is guided by coeliac testing and additional concerning features rather than age alone.

Expected finding: Endoscopy may identify cancer, ulceration, inflammatory disease, angiodysplasia, coeliac disease or no cause; a negative high-quality evaluation does not end assessment if anaemia recurs or fails to respond.

^1,4

Small-bowel and renal-tract assessment for recurrent or refractory disease

After acceptable negative upper and lower GI evaluation, inadequate response or recurrent iron-deficiency anaemia should prompt specialist assessment of the small bowel and renal tract. Capsule endoscopy is preferred for mucosal small-bowel lesions; CT or MR enterography is complementary or an alternative when capsule endoscopy is unsuitable.

Expected finding: Angioectasia, Crohn disease, tumour, renal pathology or no cause may be found; persistent anaemia after negative capsule endoscopy needs a renewed clinical assessment.

Management

Step	Detail	Source
Assess severity and arrange urgent care when physiology or symptoms demand it	Treat chest pain, syncope, breathlessness at rest, heart failure, haemodynamic instability or active bleeding as urgent problems rather than routine outpatient iron deficiency. Stabilise the patient, obtain senior or emergency assessment and investigate the source in parallel. Haemoglobin is important, but symptoms, rate of fall, comorbidity and ongoing bleeding determine urgency.^6,1	NICE NG24 Blood transfusion; BSG adult iron-deficiency-anaemia guidance
Start oral iron after confirming iron deficiency	Do not usually wait for all investigations before starting iron, unless colonoscopy is imminent. BSG recommends one tablet daily of ferrous sulphate, ferrous fumarate or ferrous gluconate initially; if not tolerated, consider one tablet on alternate days, another oral preparation or specialist-directed parenteral iron. Follow the product information and BNF for the exact preparation, elemental iron content, administration and interactions.^1,5	BSG adult iron-deficiency-anaemia guidance; BNF ferrous sulfate
Find and treat the mechanism of iron loss or failure	Address heavy menstrual bleeding, dietary deficiency, NSAID or anticoagulant-associated bleeding, gastrointestinal disease, coeliac disease, renal disease, inflammatory disease or previous gastric or bariatric surgery as appropriate. Treating a presumed menstrual or dietary cause does not remove the need for a higher-risk gastrointestinal pathway when age, sex, symptoms or response make that necessary.^1,2,3	BSG adult iron-deficiency-anaemia guidance; NICE NG20; NICE NG88
Use the current NICE FIT pathway without false reassurance	Offer quantitative FIT to adults with iron-deficiency anaemia in line with NICE NG12. A result at or above the current NICE cut-off supports suspected colorectal-cancer pathway referral. If the sample is not returned or is below the cut-off, safety-net and do not delay secondary-care referral when symptoms persist or clinical concern is strong.⁴	NICE NG12, Suspected cancer: recognition and referral
Arrange appropriate upper and lower gastrointestinal assessment	In men and postmenopausal women with newly diagnosed iron-deficiency anaemia, BSG generally recommends gastroscopy and colonoscopy as first-line GI investigations; CT colonography is a reasonable alternative when colonoscopy is unsuitable. In younger menstruating women, investigate after coeliac screening when there are additional concerning features such as severe or recurrent anaemia, gastrointestinal symptoms, weight loss, family history or disproportionate findings.^1,4	BSG adult iron-deficiency-anaemia guidance; NICE NG12
Confirm and manage coeliac disease correctly	Keep the patient on a gluten-containing diet while serology is performed. Request total IgA and IgA tissue-transglutaminase as first choice, use the IgA-deficiency pathway when needed, and refer positive adult serology to a gastrointestinal specialist for confirmation. Do not label a patient coeliac or start a lifelong gluten-free diet from an isolated screening result.²	NICE NG20, Coeliac disease: recognition, assessment and management
Monitor early response and continue long enough to replete stores	Check haemoglobin response within the first 2 to 4 weeks and investigate non-response promptly. A rise of at least 10 g/L by 2 weeks is strongly supportive of absolute iron deficiency. Continue iron for around 3 months after haemoglobin normalises to replenish marrow stores, following the selected preparation and local monitoring pathway.¹	BSG adult iron-deficiency-anaemia guidance
Use intravenous iron when oral treatment is unsuitable or inadequate	Consider parenteral iron when oral iron is contraindicated, ineffective, not tolerated, unlikely to work because of malabsorption or ongoing significant loss, or correction is particularly urgent. Confirm the preparation, dose, infusion precautions and monitoring requirements from the current BNF, product information and local infusion policy.^1,5	BSG adult iron-deficiency-anaemia guidance; BNF ferrous sulfate
Transfuse selectively, then still replace iron	Limited red-cell transfusion may be needed for symptomatic severe anaemia or urgent clinical compromise, but transfusion does not correct iron depletion. NICE NG24 recommends a restrictive threshold of 70 g/L with a post-transfusion target of 70 to 90 g/L for patients without major haemorrhage or acute coronary syndrome; consider 80 g/L with a target of 80 to 100 g/L in acute coronary syndrome. For adults without active bleeding, use single-unit transfusion with reassessment and repeat haemoglobin.^6,1	NICE NG24 Blood transfusion; BSG adult iron-deficiency-anaemia guidance
Escalate refractory or recurrent iron-deficiency anaemia	Check adherence, administration, ongoing menstrual or gastrointestinal loss, malabsorption, coeliac disease, inflammation, renal disease, haemolysis, B12 or folate deficiency and marrow pathology. If high-quality bidirectional endoscopy is negative but response is inadequate or anaemia recurs, assess the small bowel and renal tract; long-term iron may be appropriate when the cause is irreversible or remains unidentified after appropriate evaluation.¹	BSG adult iron-deficiency-anaemia guidance
Follow up the blood count and safety-net the patient	After haemoglobin and iron stores recover, monitor periodically for recurrence and ensure the result of every investigation is acted upon. Provide return advice for worsening breathlessness, chest pain, syncope, overt GI bleeding, progressive weight loss, dysphagia, persistent abdominal symptoms or treatment intolerance.^1,4	BSG adult iron-deficiency-anaemia guidance; NICE NG12

Illustrations

Blood film in iron-deficiency anaemiaPeripheral blood film showing microcytic, hypochromic red cells with anisopoikilocytosis and pencil cells; correlate with iron studies because microcytosis is not specific.E. Uthman, MD, Wikimedia Commons · CC-BY-SA-2.0

KoilonychiaPhotograph of spoon-shaped, brittle fingernails associated with chronic iron deficiency; clinical signs are supportive rather than diagnostic.CHeitz, Wikimedia Commons · CC-BY-2.0

Mechanisms of iron deficiencyDiagram mapping chronic blood loss, increased demand, poor intake and impaired absorption to the clinical causes of iron-deficiency anaemia.PassFinals · original

Differentials

Anaemia of inflammation or chronic disease

Inflammatory context with low serum iron but ferritin normal or raised and transferrin low or normal; mixed deficiency can occur.

Thalassaemia trait

Microcytosis disproportionate to the haemoglobin reduction, relatively preserved or raised red-cell count and normal iron stores.

Sideroblastic or marrow disease

Dimorphic or abnormal film, unexplained cytopenias or iron overload pattern requiring haematology assessment.

Vitamin B12 or folate deficiency

Usually macrocytosis, but mixed deficiencies can produce a deceptively normal MCV; check when the response is unexpected.

Chronic kidney disease

Renal impairment with anaemia that may be normocytic and multifactorial; iron deficiency can coexist and needs separate assessment.

Ongoing occult gastrointestinal or urinary blood loss

Recurrent or unexplained deficiency, overt bleeding, altered bowel habit, weight loss, urinary abnormalities or a higher-risk age or sex group.

Complications

Severe symptomatic anaemia, myocardial strain or high-output cardiac failure
Reduced exercise tolerance, concentration and quality of life
Adverse maternal or fetal outcomes when deficiency is significant in pregnancy
Persistent or recurrent deficiency from untreated bleeding or malabsorption
Delayed diagnosis of gastrointestinal, renal or other serious disease

Prognosis

Haemoglobin usually improves with effective iron replacement, but prognosis depends on identifying and treating the cause. Recurrent or refractory anaemia after appropriate investigation needs renewed assessment rather than indefinite empiric treatment alone.

Guidelines

Guidelines for the management of iron deficiency anaemia in adults (British Society of Gastroenterology, 2021)
Suspected cancer: recognition and referral (NG12) (NICE, 2025)
Coeliac disease: recognition, assessment and management (NG20) (NICE, 2015)

References

Evidence checked: 2026-08-03

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.