Normocytic Anaemia

Normocytic anaemia is anaemia (haemoglobin under 130 g/L in men, 120 g/L in non-pregnant women, 110 g/L in pregnancy) with a mean corpuscular volume of 80 to 100 fL. It reflects either early nutritional deficiency, loss or destruction of red cells, or underproduction by the marrow, and often has more than one cause.

• Causes of increased loss or destruction (reticulocytes raised): acute blood loss (gastrointestinal bleed, trauma, surgery, obstetric haemorrhage) and haemolysis (autoimmune haemolytic anaemia, sickle cell disease, G6PD deficiency, hereditary spherocytosis, malaria, mechanical valves, microangiopathic haemolytic anaemia, drugs).
• Causes of underproduction (reticulocytes low): anaemia of chronic disease or inflammation (infection, TB, HIV, rheumatoid arthritis, malignancy, inflammatory bowel disease), chronic kidney disease (reduced erythropoietin), endocrine disease (hypothyroidism, hypopituitarism, hypogonadism, Addison disease), early iron, B12 or folate deficiency, mixed deficiencies, bone marrow failure or infiltration (aplastic anaemia, myelodysplasia, leukaemia, lymphoma, myeloma, metastases, myelofibrosis), pure red cell aplasia (parvovirus B19), and hypersplenism.
• Dilutional anaemia of pregnancy and intravenous fluids.
• Anaemia of chronic disease is the commonest cause in hospital patients; chronic kidney disease contributes when eGFR is under 45 mL/min/1.73 m².

• Fatigue, pallor, exertional breathlessness, palpitations, headache, dizziness, reduced concentration, and in older patients angina or heart failure.
• Features of the cause: jaundice, dark urine, splenomegaly (haemolysis); melaena or haematochezia, heavy periods (blood loss); weight loss, night sweats, lymphadenopathy, fever (malignancy, TB, HIV); bone pain (myeloma); oedema and hypertension (kidney disease); cold intolerance and weight gain (hypothyroidism); joint pain and rash (connective tissue disease).
• Drug history: NSAIDs, anticoagulants, chemotherapy, antiretrovirals (zidovudine), methyldopa, penicillins, dapsone, primaquine, and herbal products.
• Travel and exposures: malaria, schistosomiasis, hookworm, TB.
• Red flags: haemoglobin under 70 g/L, haemodynamic instability, active bleeding, other cytopenias, blasts on film, haemolysis with jaundice and dark urine, kidney failure.

• FBC with differential and indices; reticulocyte count (corrected for anaemia): over 2 percent or absolute count over 100 x 10⁹/L suggests blood loss or haemolysis, whereas a low count suggests underproduction.
• Blood film: spherocytes (autoimmune haemolysis, hereditary spherocytosis), schistocytes (microangiopathic haemolysis), sickle cells, malaria parasites, rouleaux (myeloma or inflammation), leucoerythroblastic picture (marrow infiltration), blasts.
• Haemolysis screen: lactate dehydrogenase, bilirubin (unconjugated), haptoglobin (low), urine haemoglobin, direct antiglobulin (Coombs) test.
• Iron studies (ferritin, transferrin saturation, C-reactive protein), vitamin B12, folate; ferritin over 100 micrograms/L with low transferrin saturation points to chronic disease; ferritin 30 to 100 micrograms/L may represent combined iron deficiency and inflammation.
• Creatinine and eGFR, liver function, calcium, thyroid function, glucose, ESR, protein electrophoresis with serum free light chains, HIV, hepatitis, malaria film or rapid test, stool occult blood.
• Chest X-ray, abdominal ultrasound (spleen), and bone marrow aspirate and biopsy for unexplained anaemia with other cytopenias, abnormal film, or raised ESR with high globulin.
• Endoscopy or colonoscopy when gastrointestinal loss is suspected.

Treat the cause (primary strategy)

• Acute blood loss: stop bleeding, resuscitate with intravenous fluids, and transfuse; endoscopic or surgical haemostasis; proton pump inhibitor for ulcer bleeding (omeprazole 80 mg intravenous bolus, then 8 mg/hour infusion or 40 mg twice daily).
• Anaemia of chronic disease: control the infection, inflammation or malignancy; iron is given only if iron deficiency coexists; erythropoiesis stimulating agents are used in selected patients (chemotherapy related anaemia, chronic kidney disease).
• Malaria: artemether lumefantrine 4 tablets (20/120 mg each) twice daily for 3 days for uncomplicated falciparum malaria in adults over 35 kg; severe malaria needs intravenous artesunate 2.4 mg/kg at 0, 12 and 24 hours then daily.
• Hypothyroidism: levothyroxine; hypopituitarism and Addison disease: hormone replacement.
• Nutritional deficiencies: iron (ferrous sulfate 200 mg daily or alternate days), B12 (hydroxocobalamin 1 mg intramuscularly), and folate (folic acid 5 mg daily).

Chronic kidney disease

• Correct iron deficiency first (target ferritin over 100 micrograms/L, transferrin saturation over 20 percent; intravenous iron preferred in dialysis).
• Erythropoiesis stimulating agents when haemoglobin is under 100 g/L: epoetin alfa 50 to 100 IU/kg subcutaneously three times weekly (or 50 IU/kg once weekly to start), or darbepoetin alfa 0.45 micrograms/kg subcutaneously once weekly, adjusting every 4 weeks to keep haemoglobin 100 to 110 g/L and not exceeding 115 g/L (higher targets increase stroke, thrombosis and mortality); monitor blood pressure (hypertension), haemoglobin every 2 to 4 weeks, and for pure red cell aplasia. Avoid in uncontrolled hypertension and active malignancy without specialist advice.

Haemolysis

• Folic acid 5 mg orally daily for all chronic haemolysis.
• Warm autoimmune haemolytic anaemia: prednisolone 1 mg/kg orally daily (maximum 80 mg) until haemoglobin stabilises, then taper slowly over 2 to 3 months; rituximab 375 mg/m² weekly for 4 weeks if refractory or relapsed (specialist); transfuse only when necessary; avoid drugs that trigger haemolysis in G6PD deficiency (primaquine, dapsone, nitrofurantoin, sulfonamides, rasburicase).
• Sickle cell disease and microangiopathic haemolysis: specialist care.

Transfusion

• Restrictive thresholds: transfuse red cells at haemoglobin under 70 g/L (under 80 g/L in cardiovascular disease or orthopaedic surgery; under 100 g/L in acute coronary syndrome with ischaemia); give one unit at a time, reassess clinical status and haemoglobin, and avoid in stable chronic anaemia unless symptomatic or compromised.
• Avoid unnecessary transfusion in chronic kidney disease to reduce sensitisation.

Follow up

• Repeat FBC in 2 to 4 weeks after starting treatment; reassess diagnosis if no response by 4 to 6 weeks; refer to haematology for unexplained anaemia, other cytopenias, suspected marrow disease, haemolysis, or refractory anaemia.

Special groups

• Pregnancy: treat iron, folate and B12 deficiency; distinguish dilutional anaemia (haemoglobin above 105 g/L in the second trimester is physiological); treat malaria promptly; haemoglobin under 70 g/L needs admission.
• Older adults: look for occult gastrointestinal bleeding, myelodysplasia, myeloma, and kidney disease; unexplained anaemia needs full evaluation.