Sample Quality

Check the interval between phlebotomy and testing: red cells swell in vitro especially in warm weather

An interval >18 hours between venepuncture and testing  merits repeat ensuring the sample arrives in the lab as soon as possible


Common causes

  • Drugs

Check all the medications especially for antimetabolites (methotrexate, hydroxycarbamide etc)

If the patient takes an agent known to cause macrocytosis then further investigation may not be required

  • Alcohol

If there is known alcohol misuse then further investigation may not be required

  • Liver pathology

If there is a known liver diagnosis then further investigation may not be required

  • B12/folate deficiency

B12 or folate deficiency may rarely  present as macrocytosis without anaemia

Take a dietary and GI history and assess for neurology

  • Hypothyroidism

  • Myelodysplastic syndrome (MDS)

MDS may rarely present as macrocytosis without anaemia or other cytopenias

  • Reticulocytosis

Reticulocytes (immature red blood cells) are larger than mature red cells and may increase the MCV if present in sufficient quantity. They rise in response to haematinic replacement , bleeding and haemolysis

  • Raised Plasma Viscosity

Increased viscosity through inflammation or paraprotein may cause Rouleaux (red cells sticking together in-vitro) which gives an artefactually raised MCV



FBC, blood film and reticulocyte count

LFT, TSH, B12 and folate

Check immunoglobulins if the total protein is raised, there is hypercalcaemia or unexplained renal impairment.


Who to refer?

If the common causes above are absent and the patient is elderly, early myelodysplasia is possible or even likely. If the patient is not symptomatic with anaemia then referral is not necessary, though we suggest check an annual FBC to assess the trend.


Useful article:

BMJ Guidance https://www.bmj.com/content/335/7625/884



Dr Richard Noble, Consultant Haematologist, RCHT

Dr Bridgitte Wesson, GP & Kernow RMS Haematology guideline lead


Review date: 13/07/2020

Next Review 13/07/2021