We studied peripheral blood erythrocyte parameters and HFE genotypes in 94
hemochromatosis probands and 132 white, normal control subjects. Mean red blood cell counts in probands and control subjects were not significantly different. However, mean values of
hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were significantly higher in C282Y/C282Y probands (n = 60) than in wild-type control subjects (n = 65). Probands with other HFE genotypes also had increased mean erythrocyte parameters (other than red blood cell count). Peripheral blood smears prepared before therapeutic phlebotomy revealed that erythrocytes in many probands had increased diameters and were well filled with
hemoglobin. Erythrocyte parameters were similar in C282Y/C282Y probands with and without
hepatomegaly, elevated serum concentrations of hepatic
enzymes,
hepatic cirrhosis,
diabetes mellitus,
arthropathy, or
hypogonadism. Among C282Y/C282Y probands, significantly greater values of MCV (but not other erythrocyte parameters) occurred among those who had
transferrin saturation values of 75% or greater or
iron overload at diagnosis. After
iron depletion, the mean MCV, MCH, and MCHC values of C282Y/C282Y probands decreased but remained significantly greater than values in wild-type control subjects. Mean values of prephlebotomy MCH and MCHC concentrations were lower in HLA-A3-positive than in HLA-A3-negative C282Y/C282Y probands. We conclude that increased values of mean
hemoglobin, hematocrit, MCV, MCH, and MCHC in
hemochromatosis probands are caused primarily by increased
iron uptake and
hemoglobin synthesis by immature erythroid cells. Mechanisms of
iron uptake by erythrocytes that could explain these results are discussed.