Polycythemia in Patients With Hereditary Hemochromatosis: Real or Myth?

backgroundHereditary hemochromatosis (HH) is an autosomal recessive disorder affecting iron metabolism, resulting in iron accumulation in tissue parenchymal cells. Missense mutations result in homozygosity or heterozygosity for substitutions in the HFE gene, with the most common being C282Y and H63D.

methodsWith an aim to evaluate an association between polycythemia and HH, retrospective chart review was performed for 152 patients with known HFE mutations. Parameters reviewed included individual HFE genotypes, gender distribution, hemoglobin (Hgb) and hematocrit (Hct) levels, median ferritin levels and whether or not phlebotomy was required.

resultsOf 152 patients, 96 (63.2%) were men and 56 (36.8%) were women. Median Hgb and Hct were noted to be higher in men compared to women irrespective of HFE status. Mean age was 60.5 years (range 22 - 93 years). Regarding HFE mutation, 44 (28.9%) patients were C282Y/C282Y, 10 (6.6%) were H63D/H63D and 27 (17.8%) had one copy of each mutation. One patient in the study group was H63D/S65C. Median Hgb and Hct were noted to be 15.5 g/dL and 44.9% respectively in C282Y/C282Y subjects, 16.0 g/dL and 47% in H63D/H63D subjects, 15.8 g/dL and 46% in C282Y/H63D subjects, 16g/dL and 47% in those with single C282Y mutation and 16.6g/dL and 48% in those with single H63D mutation. A total of 67.1% subjects received phlebotomy. A total of 21.7% patients in this cohort were active tobacco users and only 8.6% had an established pulmonary diagnosis, including obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). Elevated Hgb levels were noted despite absence of an established reason for secondary polycythemia. Anemia was not encountered despite concurrent medical conditions that would usually be associated with anemia, including gastrointestinal bleeding or end-stage renal disease (ESRD).

conclusionsElevated Hgb and Hct levels in HH may be secondary to increased iron uptake by erythroid cell precursors in the bone marrow, in setting of increased availability of both transferrin-bound as well as non-transferrin-bound iron (NTBI). Additional studies need to be pursued to explore the association between HFE mutations and secondary polycythemia.