Two numbers organise everything
MCV gives the differential. Reticulocyte count tells you whether the problem is production or loss.
- Low reticulocytes → the marrow is not producing: deficiency, marrow disease, chronic disease, renal failure
- High reticulocytes → the marrow is responding to loss: bleeding or haemolysis
Microcytic (MCV < 80)
| Ferritin | TIBC | Transferrin saturation | |
|---|---|---|---|
| Iron deficiency | Low | High | Low |
| Anaemia of chronic disease | Normal or high | Low | Low |
| Thalassaemia | Normal | Normal | Normal |
| Sideroblastic | High | Normal | High |
Ferritin is an acute phase reactant, so a "normal" ferritin does not exclude iron deficiency in inflammation — a saturation below 20% still suggests it.
Thalassaemia trait is suggested by a disproportionately low MCV for a mild anaemia with a normal or raised red cell count; confirm with haemoglobin electrophoresis.
Iron deficiency in an adult is a symptom, not a diagnosis. In men and postmenopausal women it is gastrointestinal blood loss until proven otherwise, and the answer is endoscopic investigation, not just iron tablets.
Macrocytic (MCV > 100)
Megaloblastic — impaired DNA synthesis, with hypersegmented neutrophils:
- B12 deficiency: pernicious anaemia, ileal disease or resection, vegan diet, metformin, prolonged PPI use. Causes neurological disease — subacute combined degeneration, peripheral neuropathy, cognitive change — which can precede the anaemia
- Folate deficiency: dietary, alcohol, pregnancy, methotrexate, phenytoin
Never treat with folate alone when B12 status is unknown. Folate corrects the anaemia while the neurological damage progresses irreversibly.
Non-megaloblastic: alcohol, liver disease, hypothyroidism, myelodysplasia, reticulocytosis itself, and drugs (hydroxyurea, azathioprine, zidovudine).
Normocytic
- Anaemia of chronic disease, chronic kidney disease (erythropoietin deficiency)
- Acute blood loss — the MCV has not had time to change
- Haemolysis
- Marrow infiltration or aplasia
- Mixed deficiencies, where a high and low MCV average out
Confirming haemolysis
The panel: raised LDH, raised unconjugated bilirubin, low haptoglobin, raised reticulocytes.
Then split it:
- Direct antiglobulin (Coombs) test positive → immune. Warm (IgG — lymphoproliferative, lupus, drugs) or cold (IgM — Mycoplasma, EBV)
- Coombs negative → non-immune: microangiopathy (schistocytes — TTP, HUS, DIC, mechanical valve), membrane defects (spherocytosis), enzyme defects (G6PD), haemoglobinopathies (sickle cell)
Schistocytes with thrombocytopenia demand an urgent decision: TTP needs plasma exchange the same day, and giving platelets can make it worse.