Hypochromic Anaemia

Blood Film Appearance

Causes

Iron Deficiency Anaemia — The Most Common Form

Definition

Epidemiology

• Prevalence ~1–2% in men; much higher in women
• Menstruation causes average loss of 35 mL blood / 16 mg iron per cycle; iron requirements in women average 1–3 mg/day
• Bone marrow iron stores are absent in ~25% of healthy college-age women
• Pregnancy requires ~900 mg iron; requirements rise to 6 mg/day in the third trimester
• After menstruation, gastrointestinal (GI) bleeding is the second leading cause
• GI cancer (especially colon, gastric) found in up to 10% of older patients with IDA
• Higher incidence in developing countries (inadequate bioavailable dietary iron)

Iron Physiology & Pathobiology

• Heme iron (meat, Fe²⁺): absorbed via a specific heme receptor at 30–40% efficiency
• Non-heme iron (plant-based, Fe³⁺): reduced by stomach acid to Fe²⁺, absorbed via divalent metal transporter 1 (DMT1) — far less efficient

• Absorbed iron is exported from enterocytes via ferroportin (SLC40A1) → binds transferrin (carries up to 2 iron atoms) → delivered to marrow transferrin receptors
• Excess iron stored in ferritin (24-subunit shell, stores up to 4,000 iron molecules) in liver and macrophages
• The iron recycling cycle is >95% efficient

• Liver-derived peptide that binds and degrades ferroportin
• When hepcidin is elevated (e.g. in inflammation): iron cannot be released from enterocytes or hepatocytes → iron-restricted erythropoiesis
• Iron deficiency and hypoxia suppress hepcidin → increase iron absorption
• Inflammation upregulates hepcidin → this is the mechanism behind anaemia of chronic disease

Causes of Iron Deficiency

1. Blood loss — menstrual, GI (peptic ulcer, cancer, H. pylori, NSAIDs, IBD), haematuria
2. Reduced absorption — coeliac disease, H. pylori-associated achlorhydria, gastrectomy, proton pump inhibitor use
3. Increased requirements — pregnancy, infancy, adolescence
4. Inadequate intake — vegetarian/vegan diets (non-heme iron less bioavailable)

Clinical Features

• Fatigue, dyspnoea on exertion, pallor, palpitations, headache

• Koilonychia (spoon-shaped nails)
• Angular cheilitis and glossitis
• Pica (craving for non-food substances: ice [pagophagia], clay, starch)
• Alopecia
• Dysphagia (Plummer-Vinson / Patterson-Brown-Kelly syndrome: post-cricoid web)

Laboratory Investigations

• Ferritin is the most sensitive and specific single test for IDA; < 15 µg/L is diagnostic
• Both IDA and AI have low serum iron — the difference is TIBC (elevated in IDA, low/normal in AI) and ferritin (low in IDA, normal/elevated in AI)
• Bone marrow biopsy showing absent Prussian-blue stainable iron is the gold standard but rarely needed
• If basophilic stippling is present with normal/high serum iron → suspect thalassaemia → check Hb electrophoresis, HbA₂, HbF, and family studies
• Ring sideroblasts on bone marrow Prussian blue → sideroblastic anaemia (consider isoniazid, lead, MDS)

Treatment

Iron Deficiency

• Ferrous sulphate 325 mg (65 mg elemental iron) once or twice daily is first-line
• Vitamin C enhances absorption; milk, antacids, PPIs, and tannins reduce it
• Side effects: constipation, nausea, dark stools (common causes of non-compliance)
• Reticulocyte response begins within 3–5 days; haemoglobin normalises in 4–8 weeks
• Stores must be replenished: continue therapy for 3–6 months after Hb normalises

• Oral iron is not tolerated
• Malabsorption (coeliac disease, post-gastrectomy)
• Ongoing rapid blood loss exceeds oral replacement capacity
• Inflammatory bowel disease
• Renal failure on erythropoietin therapy

Anaemia of Chronic Disease / Inflammation

• Treat the underlying condition
• Intravenous iron if functional deficiency confirmed
• Erythropoiesis-stimulating agents (EPO) in selected cases (renal disease, chemotherapy)

Thalassaemia

• Genetic counselling; trait carriers are usually asymptomatic with mild microcytosis
• Do not give iron unless concurrent IDA is confirmed (iron supplementation is harmful in thalassaemia major)
• Severe forms require regular transfusions and iron chelation therapy

Sideroblastic Anaemia

• Pyridoxine (vitamin B₆) for hereditary/isoniazid-induced forms
• Remove offending drugs or toxins (lead chelation if lead poisoning)
• MDS-associated: supportive care ± disease-modifying therapy

Summary Algorithm

Hypochromic/microcytic anaemia (↓MCV, ↓MCH)
        │
        ├─ Serum ferritin < 15 µg/L → IRON DEFICIENCY ANAEMIA
        │       → Find cause (GI workup in adults)
        │       → Oral/IV iron replacement
        │
        ├─ Low serum iron + low TIBC + normal/↑ ferritin → ANAEMIA OF INFLAMMATION
        │       → Treat underlying disease
        │
        ├─ Normal/↑ serum iron + basophilic stippling → THALASSAEMIA
        │       → Hb electrophoresis, HbA₂, HbF
        │
        └─ Ring sideroblasts on bone marrow → SIDEROBLASTIC ANAEMIA
                → Check drugs (INH, lead), consider MDS