Should HFE mutations be checked in polycythemic patients even at lower iron levels?

INTRODUCTION: The relationship between polycythemia and hereditary hemochromatosis (HH) has been investigated in several studies. This study aimed to evaluate the association between iron parameters and Hemochromatosis Protein (HFE) gene mutations in patients with primary or secondary polycythemia, as well as in non-polycythemic patients with elevated iron parameters.
METHODS: A total of 106 patients who were evaluated for polycythemia or underwent HFE mutation testing due to elevated transferrin saturation (TS) and ferritin levels in the hematology department between 2015 and 2022 were retrospectively reviewed.
RESULTS: The median age of the 106 patients (77 male, 29 female) was 54 years (range, 19–83). HFE gene mutations were detected in 44 patients (41.5%; 31 male, 13 female). Thirty-seven patients (35%) with Myeloproliferative Neoplasms (MPNs) were classified as Group 1, 52 (49%) with secondary polycythemia as Group 2, and 17 (16%) who underwent HFE mutation testing due to elevated TS/ferritin levels without polycythemia as Group 3. The mean TS level in Group 1 was significantly higher than in Group 2 (p=0.032). Among HFE(+) patients, mean TS was significantly higher in Group 3 compared with Group 2 (p=0.023). When all polycythemic HFE(+) patients (primary + secondary) were compared with non-polycythemic HFE(+) patients, mean TS was significantly higher in non-polycythemic patients (p=0.026).
DISCUSSION AND CONCLUSION: The relatively high frequency of HFE positivity in patients with secondary polycythemia, together with its association with lower TS levels, suggests that the possibility of HH should not be overlooked in secondary polycythemia, even at lower TS levels.

Keywords: Hemachromatosis, hemochromatosis protein (HFE), polycythemia,, transferrin