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Blood Film

Red Blood Cell Size

February 15th, 2021


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.


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.
  • Microcytosis
  • 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.


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 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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