Clinical reasoning notes. Anaemia is a sign, not a diagnosis: always ask why.
The reasoning chain: confirm anaemia → classify by red cell size (MCV) → decide whether the marrow is making too few cells or the body is losing or destroying them → find the cause (including the local ones: malaria, hookworm, HIV, sickle cell, TB) → treat the cause and replace what is missing.
1. Define
Anaemia is a haemoglobin below normal for age and sex: roughly below 13 g/dL in men, 12 g/dL in women, 11 g/dL in pregnancy and young children (WHO). Symptoms: tiredness, breathlessness, palpitations, headache, pallor, and angina or heart failure when severe.
2. Classify by MCV, then by mechanism
| Type | MCV | Common causes |
|---|---|---|
| Microcytic | below 80 fL | Iron deficiency (commonest), thalassaemia, anaemia of chronic disease, sideroblastic anaemia, lead |
| Normocytic | 80–100 fL | Anaemia of chronic disease, acute blood loss, haemolysis, chronic kidney disease, marrow failure, mixed deficiencies |
| Macrocytic | above 100 fL | Vitamin B12 or folate deficiency, alcohol, hypothyroidism, liver disease, drugs (zidovudine, methotrexate, hydroxycarbamide), myelodysplasia |
Then ask: is the reticulocyte count high or low?
- High: the marrow is responding: blood loss or haemolysis.
- Low: the marrow is not making enough: deficiency, chronic disease, marrow failure or infiltration.
3. Investigate with purpose
| Test | The question it answers |
|---|---|
| Full haemogram with MCV and red cell indices | Is it anaemia, and what type? Are other lines affected? |
| Blood film | Hypochromic cells (iron deficiency), target cells (thalassaemia), sickle cells, spherocytes, schistocytes, parasites, blasts |
| Reticulocyte count | Is the marrow responding? |
| Ferritin, iron studies | Iron deficiency (low ferritin); a raised ferritin can hide deficiency in inflammation |
| B12 and folate | Macrocytic anaemia |
| Bilirubin, LDH, haptoglobin, direct Coombs test | Haemolysis? Autoimmune? |
| Haemoglobin electrophoresis | Sickle cell disease, thalassaemia |
| Malaria test, HIV test, stool for ova (hookworm) | Local causes |
| Urea, creatinine, liver and thyroid tests | Chronic kidney, liver or thyroid disease |
| Bone marrow aspirate and biopsy | Marrow failure, infiltration, myelodysplasia, leukaemia, myeloma |
| Endoscopy, colonoscopy, or stool occult blood | In an adult with iron deficiency, find the bleeding site until proved otherwise |
Where results can mislead: ferritin is an acute-phase reactant, so a "normal" level in an inflamed patient may still mean deficiency (use transferrin saturation); the haemoglobin falls late after an acute bleed (the concentration is unchanged at first); mixed deficiencies (iron plus B12) can give a normal MCV.
4. Causes by mechanism: the local list
- Blood loss: hookworm and schistosomiasis, peptic ulcer, heavy menstrual bleeding, postpartum haemorrhage, colorectal cancer.
- Haemolysis: malaria (including blackwater fever), sickle cell disease, G6PD deficiency (after drugs such as primaquine, dapsone or fava beans), autoimmune haemolysis, thalassaemia.
- Under-production: iron, folate or B12 deficiency, HIV, TB, chronic kidney disease, malignancy, aplastic anaemia.
5. Management
- Treat the cause (deworm, stop the bleeding, treat malaria and infection, start ART, treat the underlying disease).
- Replace what is missing:
- Iron deficiency: oral iron (continue 3 months after the haemoglobin normalises, to refill stores); IV iron when oral iron fails or is not tolerated, in pregnancy, or in kidney disease.
- B12 deficiency: B12 injections (oral for dietary lack only). Give folate only if B12 is replaced or absent, or neurological damage can worsen.
- Folate deficiency: folic acid.
- Transfuse only when needed: severe anaemia with heart failure, shock, ongoing bleeding, or very low haemoglobin with symptoms. In chronic anaemia, transfuse slowly (with a diuretic) to avoid overload.
- Special groups: sickle cell disease (hydroxycarbamide, folate, vaccines, prompt treatment of crises), pregnancy (iron and folate supplements), chronic kidney disease (erythropoietin).
6. When to worry
Anaemia with fever, bleeding, bruising or abnormal white cells or platelets suggests leukaemia or marrow failure: get a film and urgent haematology help.
Examiner questions
- Classify anaemia by MCV and give two causes of each.
- A man of 60 has iron deficiency anaemia. What must you do next?
- Why is giving folate alone dangerous in B12 deficiency?
Practice questions
1. A woman has MCV 65 fL, low ferritin and heavy periods. The most likely diagnosis is: A. Thalassaemia trait · B. Iron deficiency anaemia · C. Anaemia of chronic disease · D. B12 deficiency · E. Aplastic anaemia Answer: B.
2. Raised reticulocytes, raised indirect bilirubin and low haptoglobin indicate: A. Iron deficiency · B. Marrow failure · C. Haemolysis · D. B12 deficiency · E. Chronic kidney disease Answer: C.
3. A man of 62 has a haemoglobin of 8 g/dL and iron deficiency. The most important next step is: A. Iron tablets only · B. Folate · C. Blood transfusion · D. Look for a source of gastrointestinal blood loss · E. Reassure Answer: D.
4. Which drug can cause haemolysis in G6PD deficiency? A. Amoxicillin · B. Primaquine · C. Paracetamol · D. Amlodipine · E. Omeprazole Answer: B.