Elevated MCV in Patients with Hereditary Hemochromatosis.

Background: Previous studies have reported that patients with Hereditary Hemochromatosis have higher red cell volumes than normal controls. The relationship of this abnormality to the degree of iron overload and to HFE genotype has not been systematically studied.

Method: We retrospectively compared the mean corpuscular volume (MCV) of patients with Hereditary Hemochromatosis with that of an age-, race- and sex-matched control population from the primary care clinic at our institution. We studied the relationship of MCV at diagnosis with serum transferrin saturation, serum ferritin level, phlebotomy-mobilizable iron stores and HFE genotype in our patients.

Results: The study population included 290 patients who were treated for Hereditary Hemochromatosis at our center. 122/290 were homozygous for C282Y; the mean MCV of this group was significantly elevated at 95.2 fL (control group was 89.2 fL; p<0.001) Among all patients with phlebotomy-mobilizable iron greater than four grams, regardless of HFE genotype, the mean MCV was 94.8 fL (significantly greater than control, p<0.001); there was no significant difference between those who are homozygous for the C282Y HFE mutation and those who are not. Among C282Y homozygous individuals, there was no significant correlation between the MCV versus serum transferrin saturation, serum ferritin and phlebotomy-mobilizable iron (r= 0.07, 0.207 and −0.005 respectively). In patients with mobilizable iron greater than four grams who were not C282Y homozygous there was weak correlation between the MCV versus serum transferrin saturation and serum ferritin (r= 0.39 and 0.37 respectively) and no significant correlation versus phlebotomy-mobilizable iron (r= 0.04).

Conclusion: Our study confirms the presence of elevated MCV levels in patients with Hereditary Hemochromatosis. The mean MCV was high in both C282Y homozygous individuals as well as those with elevated levels of body iron (>4 g) who were not homozygous for the C282Y HFE mutation. For the most part, the elevated MCV did not correlate with measures of body iron stores although there was a weak correlation with serum transferrin saturation and serum ferritin among iron-loaded individuals who were not homozygous for C282Y. Further studies of the factors that influence MCV in these patients may provide insights into the derangements of iron utilization that may occur in iron overload syndromes.