Iron deficiency anaemia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Iron deficiency progresses from depleted stores to iron-restricted erythropoiesis and finally anaemia. Symptoms include fatigue, exertional breathlessness, palpitations, headache, impaired concentration, pica and restless legs; examination may show pallor, angular cheilitis, glossitis and nail change. None is specific, and severity depends on tempo and reserve. FBC often shows low MCV and MCH with high RDW, but early deficiency is normocytic and thalassaemia or mixed B12 deficiency can alter the expected pattern.

Ferritin is the central storage marker, interpreted alongside inflammation and liver disease. A low value strongly supports absolute deficiency; a normal value during active inflammation does not exclude it. Transferrin saturation reflects circulating iron available to marrow and can be low in both absolute and functional deficiency. The film may show hypochromia, anisopoikilocytosis and pencil cells, but morphology does not replace biochemical confirmation. A reticulocyte response and rising haemoglobin after treatment support effective delivery without proving why stores were lost.

Causal investigation prevents recurrence and missed disease. Heavy menstrual bleeding is common but should be quantified and assessed through the gynaecological pathway when abnormal. Gastrointestinal blood loss can arise from cancer, ulceration, inflammatory bowel disease, vascular lesions and medicines. Coeliac disease and upper-gastrointestinal or bariatric surgery reduce absorption. In adults with recurrent or refractory disease after appropriate endoscopy, BSG recommends further consideration of small bowel and renal tract. Treatment and investigation proceed together unless instability makes haemorrhage control the immediate priority.

Key points

Confirm iron deficiency with ferritin and the inflammatory context rather than diagnosing it from microcytosis alone; early or mixed deficiency may remain normocytic.
Low ferritin is highly supportive of depleted stores, but inflammation can raise ferritin. Transferrin saturation, CRP, reticulocyte haemoglobin where available and response help when the result is equivocal.
Find the cause at the same time as starting replacement. Menstrual loss, gastrointestinal symptoms, diet, blood donation, pregnancy, medicines, bariatric surgery and coeliac risk require explicit review.
Adult men and postmenopausal women with confirmed unexplained deficiency generally require upper and lower gastrointestinal evaluation under BSG guidance, adjusted for frailty, symptoms and prior investigation.
Offer coeliac screening in confirmed adult iron deficiency anaemia and pursue small-bowel or renal-tract causes when recurrent or refractory deficiency remains unexplained after appropriate initial assessment.
Preferred initial replacement for most stable adults is one daily tablet of ferrous sulfate, fumarate or gluconate; every-other-day dosing or an alternative preparation can improve tolerance.
Check early haemoglobin response and continue treatment after haemoglobin normalises long enough to replenish stores, while modifying duration for ongoing loss or malabsorption.
Use intravenous iron when oral treatment is ineffective, not tolerated, not absorbed or too slow for the clinical need, with product-specific dosing and hypersensitivity and phosphate safety.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Chronic blood loss

Gastrointestinal, menstrual, obstetric, urinary and recurrent donation losses exceed replacement, with occult gastrointestinal bleeding particularly important in adult men and postmenopausal women.

Reduced absorption

Coeliac disease, inflammatory bowel disease, atrophic or postoperative stomach, bariatric surgery and selected medicines reduce uptake or available luminal iron.

Increased requirement

Pregnancy, adolescence, recovery from blood loss and erythropoietic treatment increase iron use and can expose marginal intake or stores.

Inadequate intake

Restricted diets, food insecurity and poor nutritional quality contribute, but isolated dietary deficiency should not be assumed when bleeding or malabsorption remains plausible.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Store depletion
Ongoing negative iron balance first exhausts ferritin-bound storage iron in liver, macrophages and marrow before haemoglobin falls.
2
Iron-restricted erythropoiesis
Insufficient transferrin-delivered iron limits haem synthesis, producing progressively smaller, less haemoglobinised red cells and rising size variability.
3
Reduced oxygen carriage
Falling haemoglobin lowers arterial oxygen content, provoking tachycardia, increased cardiac output, fatigue and exertional breathlessness during activity.
4
Tissue iron effects
Iron-dependent epithelial, muscle and neurological functions are affected, contributing to glossitis, brittle nails, pica and restless legs beyond anaemia alone.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Typical laboratory phenotype

Low haemoglobin, MCV and MCH with high RDW, low ferritin and low transferrin saturation supports absolute iron deficiency after inflammatory context is considered.

Occult gastrointestinal source

Confirmed deficiency without menstrual explanation, especially with weight loss, dysphagia, abdominal symptoms, bowel change or visible blood, requires timely gastrointestinal investigation.

Heavy menstrual loss

Flooding, clots, double protection, prolonged bleeding or iron depletion with menstrual symptoms supports chronic gynaecological loss and warrants cause-directed assessment.

Malabsorption phenotype

Coeliac symptoms, autoimmune disease, bariatric or gastric surgery, chronic diarrhoea, inflammatory bowel disease or poor oral response raises impaired absorption.

Physiological compromiseRed flag

Chest pain, syncope, heart failure, shock or severe breathlessness with rapid anaemia indicates threatened oxygen delivery or continuing bleeding, not a routine oral-iron problem.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
FBC, film and reticulocytesFirst step
Why
Define severity, morphology, mixed deficiency and marrow response.
Interpretation and limitations
Microcytic hypochromic change supports iron restriction but is not specific. Normal MCV does not exclude early or mixed deficiency, and an absent response after treatment prompts adherence, absorption and diagnostic review.
02
Ferritin, transferrin saturation and CRP
Why
Confirm depleted stores and identify inflammation that modifies ferritin.
Interpretation and limitations
A low ferritin supports absolute deficiency. When ferritin is preserved in inflammation, low saturation and the wider phenotype may support concurrent iron restriction; use laboratory and specialty thresholds rather than inventing one cut-off.
03
Coeliac serology with total immunoglobulin context
Why
Identify a common treatable malabsorptive cause in adults with confirmed deficiency.
Interpretation and limitations
Follow the NICE coeliac pathway and account for gluten restriction and IgA deficiency. Positive serology generally leads to specialist confirmation rather than a diet started before assessment.
04
Upper and lower gastrointestinal assessment
Why
Find cancer, ulceration, inflammatory disease, vascular bleeding and other sources.
Interpretation and limitations
Select endoscopy or alternatives through BSG, cancer and local pathways based on age, sex, symptoms, frailty and previous tests. Negative initial studies do not end recurrent unexplained loss.
05
Gynaecological assessment
Why
Quantify menstrual or uterine loss and identify structural or malignant pathology.
Interpretation and limitations
Use menstrual history, pregnancy context and NICE heavy-menstrual-bleeding assessment. Treating iron does not substitute for evaluating abnormal bleeding or postmenopausal bleeding.
06
Small-bowel and renal-tract evaluation
Why
Investigate recurrent or refractory deficiency after appropriate initial studies.
Interpretation and limitations
Capsule endoscopy and renal tract assessment are selected with specialists when ongoing loss or poor response remains unexplained; repeat conventional endoscopy depends on quality and interval.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Thalassaemia trait

Disproportionate longstanding microcytosis, relatively preserved red-cell number, family or ethnic history and normal iron stores favour a haemoglobin-production variant.

Anaemia of inflammation

Inflammatory disease causes iron sequestration with low circulating availability but normal or raised ferritin; absolute and functional deficiency can coexist.

Sideroblastic or marrow disease

Alcohol, medicines, myelodysplasia and inherited sideroblastic disorders can produce microcytosis or dimorphic cells with preserved or increased iron stores.

Lead toxicity

Occupational, environmental or traditional-remedy exposure with abdominal, neurological and basophilic-stippling features prompts blood lead measurement rather than empirical iron alone.

Mixed nutritional anaemia

Concurrent B12 or folate deficiency can normalise MCV and add neurological or megaloblastic features despite unequivocal iron depletion.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ConfirmProve deficiency and assess severityFirst stepAnaemia is microcytic, hypochromic, otherwise unexplained or accompanied by symptoms suggesting depleted iron.

1Obtain FBC, reticulocytes, film, ferritin, transferrin saturation and CRP, assess symptoms and haemodynamics, and compare previous haemoglobin and MCV.
2PreferredAlternativeThe preferred diagnosis uses depleted stores plus the clinical phenotype; an alternative inflammation-adjusted assessment uses saturation, specialist thresholds and treatment response when ferritin is misleading.
3EscalationEscalate active bleeding, rapid decline, chest pain, syncope or heart failure to emergency haemorrhage and transfusion assessment rather than waiting for outpatient iron studies.

02Find the sourceInvestigate loss and malabsorptionIron deficiency anaemia is confirmed and immediate physiological danger has been addressed.

1Ask about menstrual and gastrointestinal blood loss, diet, donation, pregnancy, NSAIDs, anticoagulants, urinary bleeding, bariatric surgery and coeliac or inflammatory bowel disease.
2First lineFirst-line adult investigation follows BSG and NICE: coeliac screening plus symptom-, sex- and age-appropriate gastrointestinal and gynaecological assessment; treating a plausible source does not remove the need to document resolution.
3EscalationEscalate recurrent or refractory deficiency after adequate treatment and quality initial studies to small-bowel, renal-tract or specialist haematology assessment.

03ReplaceRestore haemoglobin and storesConfirmed deficiency requires treatment while its cause is investigated or controlled.

1PreferredAlternativePreferred initial treatment for most stable adults is one daily tablet of ferrous sulfate, fumarate or gluconate; every-other-day dosing is an alternative for intolerance, with written administration advice.
2AlternativeCheck early haemoglobin response and adverse effects, continuing after normalisation to replenish stores; lack of response triggers adherence, ongoing loss, malabsorption, inflammation and alternative-diagnosis review.
3EscalationEscalate to intravenous iron when oral treatment is ineffective, not tolerated, unlikely to absorb or clinically too slow, using the exact product calculation and monitored-infusion pathway.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Provides absorbable ferrous iron to restore erythropoiesis and replenish depleted stores in stable iron deficiency.

Ferrous sulfate

A common adult BSG regimen is one 200 mg tablet by mouth once daily; if not tolerated, use one tablet every other day or another oral preparation.

Nausea, epigastric pain, constipation, diarrhoea and dark stools affect adherence. Separate from interacting medicines according to the BNF, keep away from children and investigate non-response rather than escalating indefinitely.

Provides rapid intravenous replacement when oral therapy is ineffective, not tolerated, malabsorbed or too slow for the clinical situation.

Ferric carboxymaltose (intravenous example)

Calculate the Ferinject requirement from weight and haemoglobin; an infusion must not exceed 20 mg iron/kg or 1,000 mg, and the cumulative weekly maximum is 1,000 mg.

Use trained monitored administration with resuscitation capability and observe for at least 30 minutes afterwards. Stop for hypersensitivity or extravasation; assess phosphate risk with repeated high doses and use extra caution during infection.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Cardiorespiratory strain

Severe or rapid anaemia increases cardiac output and may precipitate angina, heart failure, syncope or marked exercise limitation in vulnerable patients.

Pregnancy and developmental effects

Maternal deficiency is associated with adverse pregnancy outcomes, while childhood deficiency can impair cognition, behaviour, growth and physical performance.

Delayed cancer diagnosis

Treating haemoglobin without investigating unexplained adult deficiency can postpone detection of gastrointestinal or other occult malignancy.

Functional impairment

Fatigue, reduced concentration, pica, restless legs and reduced work or exercise capacity can persist even before anaemia becomes profound.

Recurrent deficiency

Failure to replenish stores or control ongoing loss leads to repeated anaemia and repeated treatment, sometimes obscuring a continuing pathological source.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Check clinical tolerance and an early haemoglobin response within the BSG-recommended interval; absence of improvement requires a structured cause review.
Continue therapy beyond haemoglobin normalisation to replenish stores, adjusting duration for ongoing menstrual, gastrointestinal or malabsorptive loss.
Repeat ferritin and transferrin saturation only when they answer replenishment, recurrence or inflammatory uncertainty, and avoid interpreting immediately after intravenous iron as steady state.
Confirm completion and outcome of coeliac, endoscopic, gynaecological and renal-tract investigations through a named clinician.
After intravenous iron, monitor during and after infusion under the product protocol and check phosphate in people receiving repeated high-dose ferric carboxymaltose or with recognised risk factors.
Provide recurrence safety-netting for bleeding, weight loss, dysphagia, bowel change, chest pain, syncope and worsening breathlessness.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Iron deficiency is a diagnosis and a clue

Replacement corrects substrate lack, while the causal investigation may reveal cancer, coeliac disease, abnormal uterine bleeding or medicine-related injury.

Inflammation can hide empty stores

Ferritin rises during inflammatory illness. A preserved result therefore needs saturation, CRP and clinical interpretation rather than automatic exclusion.

Microcytosis is not mandatory

Early deficiency and mixed B12 or folate deficiency may remain normocytic. A normal MCV cannot overrule depleted stores.

Response tests delivery

A haemoglobin rise supports effective absorbed iron but does not prove that ongoing blood loss has stopped or that stores are fully replaced.

Dark stools have two meanings

Oral iron commonly darkens stool, but new melaena, symptoms or haemodynamic change still needs bleeding assessment rather than reassurance from the prescription.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing iron deficiency from microcytosis without iron studies.
02
Using normal ferritin during inflammation as a definitive rule-out.
03
Starting replacement without documenting the source investigation.
04
Attributing deficiency in an adult man solely to diet.
05
Ignoring coeliac disease or bariatric surgery in poor oral response.
06
Increasing oral doses repeatedly despite intolerance and poor absorption.
07
Stopping therapy as soon as haemoglobin enters range without restoring stores.