Smoking as an independent risk factor for macrocytosis in middle-aged adults: A population-based observational study

22 Jul 2015


Mean corpuscular volume (MCV) is a measure of the average volume of red blood cells. The detection of an elevated MCV, termed macrocytosis (with or without anemia), often prompts an extensive and costly work-up for an underlying cause and/or referral to secondary care. Known determinants of macrocytosis listed in textbooks include vitamin B12 and folate deficiency, alcohol use (with or without associated liver disease), hemolysis, hypothyroidism, coeliac disease, drug use, and hematological conditions such as aplastic anemia, myelodysplasia, and myeloma.

An association between smoking and elevated MCV has been reported from a number of studies since the 1970s [1-3]. However, knowledge of this relationship, causal or otherwise, has not translated into clinical practice or been highlighted in any of the screening models for macrocytosis. In earlier research [4], which focused on the causes of hematinic deficiency in 1,207 Irish adults, we observed an unexpected independent association between smoking and macrocytosis. The current study examined the relationship between smoking and elevated MCV, with particular reference to the independence of this association of known risk factors for macrocytosis.

We conducted a cross-sectional study involving a population representative random sample of 2,047 adults aged 46–73 years (49.2% male). Details regarding the study design, sampling procedures, and methods of data collection have been reported previously [5]. Data on age, gender, education, and smoking and alcohol behaviors were gathered through a self-completed General Health Questionnaire. Blood samples, which included full blood counts, vitamin B12, folate levels, and gamma-glutamyltransferase (GGT), were analyzed on the day of sampling using automated Sysmex analysers (Sysmex Corporation, Kobe, Japan) in one accredited laboratory. Macrocytosis, was defined as an MCV level ≥99 fl. The threshold of 99 fl was chosen as it was deemed more likely to prompt investigation for an underlying cause or referral to tertiary care.

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