Microcytic Anaemia

Microcytic anaemia is anaemia (haemoglobin under 130 g/L in men, 120 g/L in non-pregnant women, 110 g/L in pregnancy and young children) with a low mean corpuscular volume (under 80 fL in adults), reflecting impaired haemoglobin synthesis.

• Causes: iron deficiency (by far the commonest, about 50 percent of all anaemia), thalassaemia trait and disease, anaemia of chronic disease (often normocytic but microcytic in some), sideroblastic anaemia, lead poisoning, and copper deficiency or zinc excess.
• Causes of iron deficiency: inadequate intake (vegetarian diets, poverty, infants), increased need (growth, pregnancy, lactation), malabsorption (coeliac disease, atrophic gastritis, Helicobacter pylori, gastric bypass, proton pump inhibitor use), and blood loss (heavy menstrual bleeding, gastrointestinal bleeding from ulcer, NSAIDs, colorectal cancer, hookworm, schistosomiasis, haemorrhoids, and urinary losses).
• Hookworm and schistosomiasis are major causes in endemic areas.
• In men and post-menopausal women, iron deficiency anaemia should be assumed to be due to gastrointestinal blood loss until proven otherwise.

• Fatigue, pallor, breathlessness on exertion, palpitations, headache, dizziness, poor concentration, restless legs, hair loss, and reduced exercise tolerance.
• Iron deficiency specific: koilonychia, angular cheilitis, atrophic glossitis, pica (craving ice, clay or starch), brittle nails, dysphagia (Plummer-Vinson web).
• Signs: conjunctival pallor, tachycardia, flow murmur, heart failure in severe or chronic cases, and in children poor growth, irritability and developmental delay.
• History: diet, menstrual bleeding, pregnancies, bleeding (melaena, haematochezia, haematuria), weight loss, bowel habit change, medicines (NSAIDs, aspirin, anticoagulants), family history of anaemia or thalassaemia, ancestry, travel, deworming history, and lead exposure.
• Red flags: gastrointestinal alarm symptoms, weight loss, abdominal mass, dysphagia, rectal bleeding, Hb under 70 g/L, or chest pain.

• FBC with indices: low haemoglobin, low MCV and mean cell haemoglobin, raised red cell distribution width (iron deficiency), normal or low red cell distribution width with a high red cell count (thalassaemia trait).
• Blood film: hypochromic microcytes, pencil cells; target cells and basophilic stippling in thalassaemia.
• Iron studies: serum ferritin under 30 micrograms/L confirms iron deficiency (under 100 micrograms/L may still indicate deficiency when there is inflammation, chronic kidney disease or heart failure); transferrin saturation under 20 percent; raised total iron binding capacity; C-reactive protein to interpret ferritin.
• Thalassaemia: the Mentzer index (MCV divided by red cell count) under 13 favours thalassaemia, over 13 favours iron deficiency; haemoglobin electrophoresis or high performance liquid chromatography (haemoglobin A2 over 3.5 percent in beta thalassaemia trait); DNA analysis for alpha thalassaemia; perform after iron repletion.
• Find the cause: coeliac serology (tissue transglutaminase IgA), H. pylori stool antigen or breath test, stool occult blood, stool microscopy for ova (hookworm, schistosomiasis), urine for schistosomiasis and haematuria, upper endoscopy and colonoscopy for men, post-menopausal women, and anyone with alarm features or age over 50, gynaecological assessment for heavy periods, pregnancy test.
• Other tests: reticulocyte count, renal and liver function, lead level (children), copper and zinc if indicated.

Oral iron (first line for iron deficiency)

• Ferrous sulfate 200 mg (65 mg elemental iron) orally once daily, or on alternate days (better absorbed and fewer side effects), taken on an empty stomach or with vitamin C (orange juice 150 mL); alternatives: ferrous fumarate 210 mg (68 mg elemental) once daily, ferrous gluconate 300 mg (35 mg elemental) twice daily, or polysaccharide iron 150 mg daily; liquid forms in children.
• Avoid taking with tea, coffee, milk, calcium, antacids, proton pump inhibitors or phytate rich foods; separate from levothyroxine and quinolone or tetracycline antibiotics by 2 to 4 hours.
• Side effects: constipation, nausea, abdominal pain, dark stools; take with food or reduce to alternate days if not tolerated.
• Expected response: haemoglobin rises 10 to 20 g/L in 2 to 4 weeks; check haemoglobin at 4 weeks (reticulocyte count peaks at 7 to 10 days); continue for 3 months after haemoglobin normalises (about 3 to 6 months in total) to replenish stores; recheck ferritin at 3 months.
• Poor response: check adherence, ongoing loss, malabsorption, wrong diagnosis (thalassaemia trait, anaemia of chronic disease), or concurrent B12 or folate deficiency.

Intravenous iron (when oral iron fails or is not tolerated)

• Indications: intolerance, malabsorption, ongoing blood loss, inflammatory bowel disease, chronic kidney disease, heart failure, severe anaemia, third trimester of pregnancy, pre-operative anaemia, or when rapid correction is needed.
• Ferric carboxymaltose 15 mg/kg (maximum 1000 mg) as a single infusion over 15 minutes; or ferric derisomaltose 20 mg/kg single infusion; or iron sucrose 200 mg intravenously over 30 minutes on 5 occasions in 14 days. Calculate the dose according to weight and haemoglobin deficit.
• Monitor for hypersensitivity (anaphylaxis is rare) for 30 minutes after infusion, hypophosphataemia (with ferric carboxymaltose), and extravasation staining; avoid in active infection.

Treat the cause

• Heavy menstrual bleeding: tranexamic acid 1 g orally three times daily for up to 4 days of the period, mefenamic acid 500 mg three times daily during menses, levonorgestrel intrauterine system, or combined oral contraceptive.
• Hookworm: albendazole 400 mg single dose (repeat after 2 weeks if heavy infection) or mebendazole 100 mg twice daily for 3 days; schistosomiasis: praziquantel 40 mg/kg single dose; H. pylori eradication; stop NSAIDs; treat coeliac disease with a gluten free diet; investigate and treat gastrointestinal cancer or ulcer.
• Dietary advice: red meat, poultry, fish, legumes, dark green leafy vegetables, fortified cereals, vitamin C-rich fruit; limit tea and coffee with meals.

Transfusion

• Reserved for haemodynamic instability, haemoglobin under 70 g/L with symptoms or cardiac disease (under 80 g/L in cardiovascular disease), or ongoing major bleeding; transfuse one unit at a time and reassess.

Thalassaemia trait and other causes

• Thalassaemia trait needs no iron unless iron deficiency is proven; give genetic counselling and partner testing before pregnancy; folic acid 5 mg daily during pregnancy.
• Anaemia of chronic disease: treat the underlying condition; lead poisoning: remove the source and chelate (succimer, specialist); sideroblastic anaemia: pyridoxine 50 to 200 mg daily for a 3 month course under haematology.

Follow up

• Review at 4 weeks (haemoglobin), 3 months (haemoglobin, ferritin), then every 3 to 6 months for a year; refer to haematology for unexplained or refractory anaemia, suspected thalassaemia, or sideroblastic anaemia.

Special groups

• Pregnancy: ferrous sulfate 200 mg once or twice daily (60 to 120 mg elemental iron) for treatment; prevention with 30 to 60 mg elemental iron daily; intravenous iron from the second trimester if oral iron fails or anaemia is severe; haemoglobin under 70 g/L, or symptomatic anaemia near term, needs admission.
• Infants and children: elemental iron 3 to 6 mg/kg/day orally (usually in one or two doses) for 3 months (for example ferrous sulfate liquid 6 mg/kg elemental iron daily divided); screen premature infants and exclusive breastfed babies after 4 to 6 months; avoid cow's milk before 12 months; deworming every 6 months in endemic areas.
• Chronic kidney disease and heart failure: intravenous iron is more effective; target ferritin over 100 micrograms/L and transferrin saturation over 20 percent.