Overview
Assessment of red blood cell size - the presence of normocytosis, microcytosis or macrocytosis - is the first step in the assessment of patients with anaemia as it can rapidly be used to narrow down the likely causes.
On a blood film, the red cell size can be assessed by comparing red cells to small lymphocytes. The nucleus of a small mature lymphocyte is slightly larger than a normal red blood cell.
Microcytosis
Microcytes are small red blood cells with mean corpuscular volume (MCV) <80 fL. On a blood film, they are significantly smaller than small mature lymphocytes.
Causes of Microcytosis
- Iron deficiency anaemia - nutritional deficiency, blood loss, malabsorption, pregnancy
- Anaemia of chronic disease (chronic infection / inflammation / malignancy)
- Thalassaemia (alpha / beta)
- Congenital sideroblastic anaemia
- Hyperthyroidism
- Lead poisoning
- Copper deficiency
Practical Points
- Microcytosis is often associated with anaemia, but not always.
- In thalassaemia, the MCV tends to be inappropriately low compared to the degree of anaemia.
Macrocytosis
Macrocytes are large red blood cells with mean corpuscular volume (MCV) >100 fL. On a blood film, they are larger than small mature lymphocytes.
Causes of Macrocytosis
Megaloblastic
- B12 deficiency
- Folate deficiency
- Drugs - methotrexate, chemotherapy, reverse transcriptase inhibitors, valproate, phenytoin, nitrous oxide, trimethoprim
Non-Megaloblastic
- Chronic liver disease
- Chronic alcohol abuse
- Post splenectomy
- Aplastic anaemia
- Myelodysplastic syndrome
- Hypothyroidism
- Reticulocytosis (haemolysis, haemorrhage, recovery post anaemia)
Practical Points
- Macrocytosis without anaemia is often normal.
- The classical findings on blood film for megaloblastic anaemia are macroovalocytes and hypersegmented neutrophils.
- Macrocytosis with polychromasia is suggestive of reticulocytosis, and haemorrhage / haemolysis should be considered.
Anisocytosis
Anisocytosis refers to increased variability of red blood cell size. Red cells are normally of uniform size, and significant variation
Look For
- Elevated Red cell distribution width (RDW) on full blood count
- Variability in red blood cell size on blood film
Anisocytosis may be caused by any condition that results in microcytosis or macrocytosis.
For example, a patient with early megaloblastic anaemia may have a mix of macrocytes and normally sized cells, resulting in an overall normal mean red cell volume (MCV) with anisocytosis.
Interpretation
- More microcytic - suggests iron deficiency or sideroblastic anaemia
- More normocytic - suggests early iron deficiency or megaloblastic anaemia, reticulocytosis (haemolysis, recovery following haemorrhage or bone suppression) or sickle cell anaemia
- More macrocytic - suggests megaloblastic anaemia, myelodysplastic syndrome or chronic liver disease
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