Anaemia Morphological Approach
On this page
Direct answer
Anaemia is classified morphologically by the mean corpuscular volume, which sorts the work-up into microcytic, normocytic and macrocytic groups before any specific test is ordered. A low MCV points to iron deficiency, thalassaemia or sideroblastic anaemia, a normal MCV to acute blood loss, anaemia of chronic disease or early iron deficiency, and a high MCV to vitamin B12 or folate deficiency, liver disease or myelodysplasia. The reticulocyte count then separates marrow failure from a hyperproliferative response, which is usually the most useful next step.
What you must remember
- MCV cut-offs: microcytic below about 80 fL, macrocytic above about 100 fL, and normocytic in between.
- Iron deficiency: low ferritin confirms it, and a raised red cell distribution width is typical of early deficiency, while the MCV falls later.
- Mentzer index: MCV divided by red cell count below 13 suggests thalassaemia trait, and a higher value suggests iron deficiency; haemoglobin electrophoresis then confirms.
- Ferritin caveat: ferritin is an acute-phase reactant, so inflammation or liver disease can mask concurrent iron deficiency.
- Reticulocyte count: a low count indicates a hypoproliferative marrow, while a high count after bleeding or haemolysis indicates a bone marrow response.
- Megaloblastic macrocytosis: hypersegmented neutrophils, serum B12 and folate levels, with methylmalonic acid when B12 is borderline.
- Non-megaloblastic macrocytosis: alcohol, liver disease, hypothyroidism, reticulocytosis and drugs such as hydroxyurea or azathioprine, and myelodysplasia.
A worked case: fatigue with a small red cell
A 34-year-old woman has fatigue, haemoglobin of 8.2 g/dL, an MCV of 68 fL, a raised red cell distribution width and a ferritin of 6 ng/mL.
- Read the iron pattern: That pattern is iron deficiency, and the next step is a cause: menstrual history, coeliac serology, and in men or postmenopausal women an endoscopy and colonoscopy.
- Compare a similar small cell: A 30-year-old with the same MCV has a red cell count of 6.0 million per microlitre and a Mentzer index of 11, below 13, so thalassaemia trait is more likely. Iron supplementation would be wrong, and haemoglobin electrophoresis settles it.
- Consider kidney disease: A third patient with a normocytic anaemia, reticulocyte count of 0.3 percent and raised creatinine points to anaemia of chronic kidney disease. A normocytic anaemia with a high ferritin and low serum iron points to anaemia of chronic disease.
- Read the values together: The shared discipline is to read the MCV, the red cell count, the reticulocyte count and the ferritin together rather than one value in isolation.
Where the examiner sets the trap
Four traps recur in examiner questions.
- Trap: giving iron to a patient with thalassaemia trait Correct: this is frequently encountered in Indian clinics and often coexists with true iron deficiency, so the Mentzer index and electrophoresis should precede treatment.
- Trap: ruling out deficiency because the MCV is normal Correct: a patient with iron deficiency and B12 deficiency can have a normal volume, so a normal MCV does not exclude deficiency.
- Trap: attributing alcohol-related macrocytosis to B12 deficiency Correct: it is non-megaloblastic and resolves with abstinence.
- Trap: accepting an analyser's macrocytosis at face value Correct: cold agglutinins can falsely raise the MCV and lower the red cell count on automated analysers, so a smear review resolves the apparent macrocytosis.
The viva answer names the first split, the reticulocyte count and the single test that changes management.
Frequently asked questions
What does a raised MCV with a low reticulocyte count suggest?
A macrocytic anaemia with a low reticulocyte count points to a marrow maturation or production problem, such as B12 or folate deficiency, myelodysplasia, or a drug effect from agents like methotrexate. The peripheral smear and B12 and folate levels distinguish these causes.
How is the Mentzer index used to separate iron deficiency from thalassaemia trait?
The Mentzer index is the MCV divided by the red cell count, and a value below 13 suggests thalassaemia trait, while a higher value suggests iron deficiency. It is a simple bedside screen that should be confirmed by haemoglobin electrophoresis before any treatment decision.
Why is a normal ferritin not always reassuring in anaemia?
Ferritin is an acute-phase reactant, so inflammation, infection or liver disease can raise it and mask concurrent iron deficiency. Serum soluble transferrin receptor or bone marrow iron staining helps resolve conflicting results.
Which test separates megaloblastic from non-megaloblastic macrocytosis?
Hypersegmented neutrophils on the smear, together with low serum B12 or folate, suggest megaloblastic macrocytosis. Alcohol, liver disease and hypothyroidism cause macrocytosis without megaloblastic change, and methylmalonic acid helps when B12 is borderline.