Key Facts

Iron deficiency anaemia results from insufficient iron to support normal erythropoiesis. In primary care, the emphasis is on identifying the underlying cause, as IDA in men and postmenopausal women may be the presenting feature of gastrointestinal malignancy.

Epidemiology

• Prevalence of IDA: 2-5% in adult men and postmenopausal women; 10-20% in premenopausal women
• Iron deficiency without anaemia is even more common (up to 30% of premenopausal women)
• Most common cause of anaemia in UK primary care
• GI malignancy is found in approximately 6-13% of patients with unexplained IDA

Aetiology

• Blood loss: menorrhagia (commonest in premenopausal women), GI blood loss (peptic ulcer, colorectal cancer, gastric cancer, angiodysplasia, NSAIDs, oesophagitis)
• Malabsorption: coeliac disease, inflammatory bowel disease, gastrectomy/bariatric surgery, H. pylori infection
• Increased demand: pregnancy, growth (children/adolescents)
• Dietary insufficiency: vegan/vegetarian diet (rare as sole cause in developed countries)

Pathophysiology

• Iron is absorbed in the duodenum and proximal jejunum, regulated by hepcidin
• Iron is transported bound to transferrin and stored as ferritin
• Depletion of iron stores leads to iron-deficient erythropoiesis and eventually microcytic hypochromic anaemia
• Stages: iron depletion (low ferritin) → iron-deficient erythropoiesis (low transferrin saturation) → iron deficiency anaemia (low Hb, microcytic)

Common Symptoms

• Fatigue and lethargy (most common)
• Shortness of breath on exertion
• Palpitations
• Pallor
• Headache and dizziness

Specific Signs of Iron Deficiency

• Koilonychia (spoon-shaped nails)
• Angular cheilitis (stomatitis)
• Glossitis (smooth, red tongue)
• Pica (craving non-food substances, e.g. ice)
• Restless leg syndrome
• Brittle hair

Symptoms Suggesting Underlying Cause

• Change in bowel habit, rectal bleeding — GI malignancy
• Heavy menstrual bleeding — menorrhagia
• Weight loss, bloating, diarrhoea — coeliac disease or GI malignancy
• Dyspepsia, epigastric pain — peptic ulcer

Red Flags

• IDA in men or postmenopausal women — exclude GI malignancy
• Weight loss
• Rectal bleeding or change in bowel habit
• Abdominal mass
• Dysphagia (consider Plummer-Vinson syndrome)
• Severe anaemia (Hb <70 g/L or symptomatic)

Bedside

• Full history including diet, medications (NSAIDs, anticoagulants), menstrual history, GI symptoms
• Examination: pallor, koilonychia, glossitis, abdominal mass, rectal examination

Bloods

• FBC: low Hb, low MCV (<80 fL), low MCH
• Ferritin: <30 mcg/L diagnostic of iron deficiency (consider <50 mcg/L if concurrent inflammation)
• Iron studies: low serum iron, low transferrin saturation (<16%), raised TIBC
• Blood film: microcytic hypochromic red cells, pencil cells, target cells
• Reticulocyte count: low or inappropriately normal
• CRP/ESR: to assess for concurrent inflammation (ferritin is acute phase reactant)
• Coeliac screen: anti-tTG IgA + total IgA (NICE NG20)
• U&Es, LFTs: baseline
• H. pylori testing: consider if dyspeptic symptoms

Imaging/Endoscopy

• Men and postmenopausal women with IDA: OGD + colonoscopy (BSG guidelines)
• CT colonography: alternative if colonoscopy declined or inappropriate
• Premenopausal women: GI investigation if GI symptoms, family history of GI cancer, failed response to iron, or age ≥50

Special Tests

• Faecal immunochemical test (FIT): may be used as part of initial assessment in primary care
• Bone marrow biopsy: rarely needed; gold standard for iron stores assessment

Non-pharmacological

• Dietary advice: red meat, green leafy vegetables, fortified cereals, dried fruit
• Vitamin C enhances iron absorption (take iron with orange juice)
• Avoid tea, coffee, calcium supplements at time of iron ingestion (inhibit absorption)
• Treat underlying cause (e.g. manage menorrhagia, treat H. pylori, gluten-free diet for coeliac)

Pharmacological

• First-line: ferrous sulphate 200mg BD-TDS (contains 65mg elemental iron per tablet)
• Alternative: ferrous fumarate 210mg BD-TDS (68mg elemental iron per tablet)
• Duration: continue for 3 months after Hb normalises to replenish iron stores
• Check Hb after 2-4 weeks: expect rise of approximately 20 g/L over 3-4 weeks
• If intolerant: try alternate day dosing, switch preparation (ferrous gluconate 300mg BD), or liquid formulations
• IV iron (ferric carboxymaltose [Ferinject] 1000mg single infusion, or iron sucrose): if oral iron not tolerated, malabsorption, ongoing blood loss, or rapid correction needed
• Blood transfusion: reserved for acute symptomatic anaemia or Hb <70 g/L with haemodynamic compromise

Surgical

• Treat underlying surgical cause (e.g. colorectal cancer resection, endoscopic treatment of angiodysplasia)

Referral Criteria

• Men and postmenopausal women with IDA: 2-week-wait referral if age ≥60 or suspected GI malignancy (NICE NG12)
• GI referral for OGD and colonoscopy in all men and postmenopausal women with IDA
• Haematology referral if no cause found after GI investigation, refractory to treatment, or suspected haematological malignancy
• Gynaecology referral for menorrhagia not responding to medical management

• Hb typically normalises within 6-8 weeks of adequate oral iron supplementation
• Ferritin normalises after 3-6 months of continued treatment
• Response failure (no Hb rise after 2-4 weeks): reassess compliance, consider malabsorption or ongoing blood loss
• GI malignancy found in 6-13% of men/postmenopausal women investigated for IDA
• With treatment of underlying cause, prognosis for IDA itself is excellent
• Untreated IDA in pregnancy associated with preterm birth and low birth weight

BSG Guidelines for Investigation of IDA

Iron Preparation Comparison