Introduction
The advent of automatic cell counters has made the red cell indices including mean cell volume (MCV) widely available. An elevated MCV (i.e. macrocytosis) can be caused by several medical conditions and a variety of drugs. In this study we have considered patients aged 75 years and above, who were found to have a raised MCV with or without anaemia. Where conventional haematological and biochemical tests failed to elucidate the cause of the elevated MCV, patients were classified as having unexplained macrocytosis. The latter group had bone marrow aspirate (+/-trephine) in an attempt to define the cause of the macrocytosis.
Patients and Methods
We studied 124 patients aged 75 years and above, who were found to have a raised MCV as defined by MCV > 95 fl when measured on a Coulter Counter STCK-R. All patients underwent full clinical assessment, paying particular attention to drug history and alcohol consumption. Clinical manifestations of disease that could be responsible for macrocytosis, e.g. hypothyroidism, are generally more difficult to evaluate in elderly people. Investigations performed on all patients included:
1. Blood film examination 2. Serum vitamin B12 3. Serum and red cell folate 4. Thyroid function tests (thyroxine and thyroid-stimulating hormone) 5. Liver function tests, including gamma glutamyl transferase.
Significant haemolysis was excluded by the examination of the blood film in association with the liver function tests. A reticulocyte count and Coombs test were only performed if indicated following the above investigations. Although reticulocytosis is often cited as a cause for a raised MCV, it is a rare cause in our experience. In a similar study, Keenan [1] reported only two cases of haemolysis in a group of 80 patients. Where these investigations failed to elucidate the cause of the raised MCV, a bone marrow examination was performed. Forty-nine patients proceeded to bone marrow examination and all had marrow aspirates. Trephine biopsy was obtained in 38 patients. In the remaining 11 patients, trephine biopsy was unsuccessful.
Marrow aspirates were examined morphologically after Giemsa staining and in addition all aspirates were stained to assess iron stores. Where a trephine biopsy was available, histological sections were examined.
Results
Out of 124 patients included in the study, the cause of the raised MCV was determined in 75 patients by non-invasive techniques (Table I). Fifteen patients were found to have hypothyroidism, in 17 patients macrocytosis was believed to be related to ethanol intake, fifteen patients had folic acid deficiency, another fifteen had vitamin B12 deficiency, and three patients had combined vitamin B12 and folate deficiency.
Table I. Diagnosis following evaluation of macrocytosis by non-invasive techniques
Furthermore, the most frequent morphological abnormalities of the red cells reported in patients with MDS are acanthocytosis and macrocytosis due to increase in cholesterol/phospholipid quotient in the red cell membrane [16].
We conclude that macrocytosis (MCV > 95 fl) is a useful and simple parameter indicative of an abnormality for which a definitive diagnosis could be reached in most cases. The probability of achieving a definitive diagnosis increases with higher degrees of macrocytosis (MCV > 100 fl). Where macrocytosis remains unexplained after all appropriate tests -- including a bone marrow biopsy -- have been performed, we believe this could be an early sign of MDS. Follow-up of patients with unexplained macrocytosis with normal or non-specific dysplastic features in bone marrow for evidence of evolution to a distinct type of MDS as classified by the F.A.B. group should help elucidate this hypothesis.
References
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Authors' addresses M. Y. Mahmoud, C. C. Anderson Department of Haematology
M. Lugon(*) Department of Elderly Medicine
Whipps Cross Hospital, Whipps Cross Road, Leytonstone, London E11 1NR
(*) Address correspondence to Dr M. Lugon
Received in revised form 5 February 1996
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