Macrocytosis: pitfalls in testing and summary of guidance

Abstract

Case 1A 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 238×109/l, and a mean red cell volume of 127 fl. As a result of the macrocytosis further investigations were done; vitamin B-12 concentration was 457 ng/l (reference range 160-700 ng/l) and red cell folate was 228 µg/l (reference range 97-570 µg/l). In view of the normal results the general practitioner requested an early appointment to investigate the cause of macrocytosis.Discussion—The level of macrocytosis can predict whether vitamin B-12 and folate deficiency is present.2 As the mean cell volume increases to more than 100 fl, the probability of vitamin B-12 and folate deficiency also increases. This is particularly true in patients with a mean cell volume >130 fl, except for those who are receiving hydroxycarbamide, as illustrated by this case. Patients who are receiving hydroxycarbamide usually have an mean cell volume >110 fl, and the level of the macrocytosis is related to the dose of hydroxycarbamide.3 Mean cell volumes of 100-110 fl are more likely to be related to other causes of macrocytosis, such as alcohol abuse, liver disease, hypothyroidism, anti-neoplastic drugs, HIV infection with the use of zidovudine, and haematological disorders such as haemolysis and myelodysplastic syndromes.2 4 A blood film is usually helpful in these cases as hypersegmented neutrophils and macro-ovalocytes are associated with vitamin B-12 and folate deficiency, a uniform macrocytosis with alcohol abuse, target cells with liver disease, and polychromasia with haemolysis.