01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Iron deficiency begins with depletion of storage iron and then restricts haem synthesis, causing anaemia that may be microcytic and hypochromic. Ferritin is the most specific storage marker when low, but inflammation can raise it; transferrin saturation and CRP help interpret an apparently normal ferritin.
The 2025 BSG and ACPGBI clarification places quantitative FIT and coeliac serology before referral for unexplained adult IDA. A result at or above 10 micrograms haemoglobin per gram directs the relevant suspected-cancer pathway for upper and lower gastrointestinal assessment. A lower result without suspicious symptoms directs urgent non-cancer secondary-care clinical assessment, which decides the appropriateness and timing of upper and lower investigation from age, haemoglobin and comorbidity rather than mandating identical immediate bidirectional testing for every adult. Missing samples must be pursued, and FIT does not remove clinically indicated upper-GI assessment.
Key points
- Confirm deficiency with ferritin and transferrin saturation interpreted beside CRP; microcytosis alone is insufficient.
- Send quantitative FIT and coeliac serology before referral in a new unexplained adult IDA pathway, while treating physiological urgency immediately.
- FIT at or above 10 micrograms per gram supports the relevant urgent cancer pathway for upper and lower GI assessment.
- Below-threshold FIT without suspicious symptoms needs urgent non-cancer secondary-care clinical assessment to decide the appropriateness and timing of upper and lower investigation from age, haemoglobin and comorbidity; actively pursue an unreturned kit.
- Use ferrous sulphate 200 mg once daily, about 65 mg elemental iron, as one practical oral starting regimen.
- Check haemoglobin response within four weeks and complete cause investigation rather than equating response with diagnosis.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Chronic blood loss
Gastrointestinal lesions, menstruation, blood donation and medication-related mucosal injury can remove small amounts of iron repeatedly.
Reduced intake or absorption
Restricted diet, coeliac disease, gastric surgery and inflammatory disorders may limit iron delivery or uptake despite the absence of bleeding.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Store depletion
Negative iron balance first lowers ferritin as reticuloendothelial and hepatic stores are consumed before circulating haemoglobin visibly falls.
- 2Restricted erythropoiesis
Insufficient available iron limits haem synthesis, eventually producing hypochromic microcytic red cells and reduced oxygen carriage.
- 3Physiological compensation
Tachycardia and increased cardiac output compensate for anaemia, but limited cardiopulmonary reserve can produce angina, dyspnoea or collapse at higher haemoglobin levels.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Low ferritin is the most specific marker of depleted iron stores, but inflammation can raise ferritin; transferrin saturation and the wider inflammatory picture help when results are equivocal.
Microcytosis supports iron deficiency but can be absent early, and other causes of microcytosis such as haemoglobinopathy should be considered in the right context.
In adult men and postmenopausal women, unexplained iron-deficiency anaemia commonly warrants examination of both upper and lower gastrointestinal tracts.
Menstrual and dietary histories matter in premenopausal women, yet disproportionate, recurrent or symptomatic anaemia still needs a cause-based assessment.
Absence of visible bleeding does not reassure because small repeated gastrointestinal losses can exhaust iron stores before stool appearance changes.
05InvestigationsWhat to request, why it matters and how to interpret it.
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
Full blood count, reticulocytes and blood filmFirst step - Why
- characterise anaemia and look for alternative or combined haematological processes
- Interpretation and limitations
- Haemoglobin severity guides urgency; mean cell volume alone cannot confirm or exclude iron deficiency.
- 02
Ferritin, transferrin saturation and C-reactive protein - Why
- confirm iron depletion and recognise inflammation-related ambiguity
- Interpretation and limitations
- A low ferritin supports deficiency; a normal or raised value during inflammation may require transferrin saturation and clinical interpretation.
- 03
Coeliac serology with total immunoglobulin A - Why
- look for malabsorptive coeliac disease as a cause of iron deficiency
- Interpretation and limitations
- IgA deficiency can make standard serology falsely negative and may require an alternative assay.
- 04
Quantitative FIT before referral - Why
- Stratify colorectal-cancer urgency in unexplained adult iron-deficiency anaemia under the 2025 BSG and ACPGBI pathway.
- Interpretation and limitations
- At least 10 micrograms haemoglobin per gram directs the relevant cancer pathway; below threshold without suspicious symptoms requires urgent non-cancer secondary-care clinical assessment to decide upper and lower investigation from age, haemoglobin and comorbidity, and non-return must be pursued.
- 05
Urinalysis and selected small-bowel or renal-tract investigation - Why
- seek non-luminal blood loss or lesions after unexplained recurrent deficiency
- Interpretation and limitations
- Further testing is driven by quality of prior assessment, response to iron and the continuing clinical pattern.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Anaemia of inflammation
Ferritin may be normal or high with reduced circulating iron; mixed absolute deficiency remains possible and requires combined biochemical interpretation.
Haemoglobinopathy
Thalassaemia trait can cause marked microcytosis with relatively preserved haemoglobin and does not respond to unnecessary iron.
Vitamin deficiency or marrow disease
Macrocytosis may be masked by combined deficiency, while pancytopenia or abnormal film features suggest broader pathology.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01Worked case: applied iron-deficiency anaemia and occult gi blood lossReach a specific decision and confirm it happenedFirst stepA 66-year-old man has fatigue, haemoglobin 92 g/L, ferritin 7 micrograms/L, normal blood pressure and no visible bleeding. Coeliac serology is negative and quantitative FIT returns 38 micrograms haemoglobin per gram.+
- 1Confirm stable physiology and absence of chest pain, syncope or breathlessness at rest, allowing an urgent outpatient rather than resuscitation pathway.
- 2Review blood count, ferritin, transferrin saturation and CRP and take medication, donation, dietary, family and gastrointestinal histories with abdominal and rectal examination.
- 3Interpret FIT 38 as above 10 micrograms per gram and refer through the relevant suspected cancer pathway for both upper and lower GI investigation; negative coeliac serology does not explain the loss.
- 4Start ferrous sulphate 200 mg once daily, about 65 mg elemental iron, because no colonoscopy is scheduled within the next two weeks and treatment should not wait for the diagnostic outcome.
- 5Verify haemoglobin response within four weeks, gastroscopy and complete colonic assessment with histology, and continue iron for about three months after haemoglobin normalises if tolerated.
02Below-threshold IDA pathwayInvestigate iron deficiency even when FIT is lowA postmenopausal adult has haemoglobin 104 g/L, ferritin 8 micrograms/L, FIT 3 micrograms per gram, no suspicious symptoms and negative coeliac serology.+
- 1Confirm a returned valid FIT sample and absence of haemodynamic or cancer alarm features; begin a defined oral iron regimen and document expected early response.
- 2Refer urgently for non-cancer secondary-care clinical assessment rather than treating the low FIT as exclusion of gastrointestinal disease. At that assessment, age, haemoglobin, comorbidity and fitness support prompt gastroscopy and complete colonic investigation for this postmenopausal adult.
- 3Verify gastroscopy, complete colonic assessment, histology and response; persistent or recurrent IDA after high-quality tests prompts small-bowel and renal-tract consideration.
03Symptomatic severe anaemia pathwayStabilise before routine replacement monitoringA patient with ongoing melaena has haemoglobin 54 g/L, pulse 124/min, chest pain, cool peripheries and systolic pressure 86 mmHg.+
- 1Call emergency help, begin ABCDE care, provide oxygen when indicated, obtain large-bore access, crossmatch, coagulation and renal tests, and activate major-haemorrhage support according to physiology.
- 2Seek urgent gastroenterology and anaesthetic review for source control and make a senior red-cell transfusion decision from shock, myocardial symptoms, bleeding and comorbidity rather than ferritin alone.
- 3Verify perfusion, chest pain, haemoglobin trend and haemostasis in a monitored setting; define iron replacement only after immediate resuscitation and bleeding control are under way.
Key medicines and prescribing safety1 treatment · regimens, roles and cautions+
Ferrous sulphate 200 mg tablet
Give one 200 mg tablet by mouth once daily, providing about 65 mg elemental iron; if gastrointestinal adverse effects prevent adherence, consider one tablet on alternate days, another oral preparation or intravenous iron according to urgency and absorption.Warn about nausea, constipation, diarrhoea and dark stool; separate from medicines and foods that reduce absorption when clinically relevant. Consider intravenous replacement when oral iron is ineffective, not tolerated or unlikely to be absorbed.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Cardiorespiratory strain
Severe anaemia can provoke angina, heart failure, dyspnoea, syncope and impaired exercise tolerance when cardiopulmonary reserve is limited.
Delayed underlying diagnosis
Correction of haemoglobin without source investigation may postpone recognition of gastrointestinal cancer or inflammatory disease while the blood count temporarily improves.
Functional impairment
Fatigue, cognitive difficulty and reduced work or exercise capacity can persist even before profound anaemia develops.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Measure early haemoglobin response; failure to rise should prompt review of adherence, continuing loss, malabsorption, inflammation or an incorrect diagnosis.
- Continue oral iron for roughly three months after haemoglobin normalises when tolerated, then confirm that stores and symptoms have recovered.
- Verify completion and quality of gastrointestinal investigation, including histology, rather than assuming a referral means the cause was excluded.
- After correction, periodic blood counts can detect recurrence, which should trigger renewed assessment rather than repeated iron without explanation.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Ferritin has context
Inflammation can conceal depleted stores behind a normal ferritin, so transferrin saturation and inflammatory markers help resolve discordant results.
Treatment and investigation run together
Replacing iron improves physiology but does not explain the loss; diagnostic work should continue while treatment is given.
Response is evidence
A measurable haemoglobin rise after iron supports absolute deficiency, whereas non-response identifies adherence, absorption or ongoing-loss problems.
Occult means unseen
Normal-looking stool cannot exclude chronic gastrointestinal bleeding from cancer, vascular lesions, inflammation or ulceration.
11Common pitfallsFrequent interpretation and management errors.
- 01
Prescribing repeated iron courses without investigating unexplained deficiency can temporarily mask a continuing malignant or inflammatory source.
- 02
Calling microcytosis diagnostic of iron deficiency overlooks thalassaemia traits and mixed anaemia.
- 03
Delaying all iron until endoscopy prolongs symptoms and is usually unnecessary unless the procedure timing or another clinical factor dictates.
- 04
Stopping replacement as soon as haemoglobin enters range may leave stores depleted and make early recurrence more likely.