Intended for healthcare professionals

Practice Cases in Primary Care Laboratory Medicine

Macrocytosis: pitfalls in testing and summary of guidance

BMJ 2007; 335 doi: (Published 25 October 2007) Cite this as: BMJ 2007;335:884
  1. Michael Galloway, consultant haematologist1,
  2. Malcolm Hamilton, consultant haematologist and organiser of the UK NEQAS scheme for haematinic assays2
  1. 1City Hospitals Sunderland NHS Foundation Trust, Sunderland Royal Hospital, Sunderland SR4 7TP
  2. 2Department of Haematology, Royal Devon and Exeter NHS Foundation Trust, Exeter EX2 5DW
  1. Correspondence: M Galloway mike.galloway{at}
  • Accepted 12 June 2007

Low vitamin B-12 levels can occur without deficiency being present, and normal levels don't always rule out vitamin B-12 deficiency. A clinical assessment, together with blood count and blood film results, can ensure a correct interpretation of vitamin B-12 and folate levels

Summary points

  • Macrocytosis is commonly associated with the use of several drugs and does not require further investigation unless there are additional clinical features

  • Before testing, the probability of vitamin-B12 or folate deficiency should be undertaken by assessing relevant features in the history and examination

  • Myelodysplastic syndromes often present as a macrocytic anaemia with normal vitamin-B12 and folate concentrations

  • When full blood count is normal, vitamin-B12 deficiency should be suspected in patients with neurological signs and severe oropharyngeal ulceration

Deficiency of vitamin B-12 and folate classically causes a macrocytic anaemia, but macrocytosis may be due to causes other than deficiency of vitamin B-12 and folate. Neurological changes due to vitamin B-12 deficiency may develop in the absence of changes in the blood count. Incorrect interpretation of vitamin B-12 levels in particular can lead to a wrong diagnosis, inappropriate referral to hospital, and inappropriate investigation. We have published guidance on the indications for requesting vitamin B-12 and folate levels and how to assess response to treatment and follow-up of these patients.1 The four cases below outline some pitfalls in investigating patients for apparent deficiency of vitamin B-12 and folate and show the value of a pragmatic approach (discussing results with a haematologist and considering a therapeutic trial of vitamin B-12).

Case 1

A 76 year old woman with a diagnosis of polycythaemia rubra vera was under the care of the haematology clinic and was being treated with hydroxycarbamide. She presented to her general practitioner with an intercurrent illness. Her blood count showed haemoglobin 137 g/l, white count 6.7×109/l, platelets 238×10 …

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