NTBI levels in C282Y homozygotes after therapeutic phlebotomy.

C282Y homozygotes exposed to sustained elevated transferrin saturation (TS) may develop worsening clinical symptoms. This might be related to the appearance of non-transferrin bound iron (NTBI) when TS≥50% and labile plasma iron (LPI) when TS levels reach 75-80%. In this study, NTBI levels were examined in 219 randomly selected untreated and treated C282Y homozygotes. Overall, 161 of 219 had TS ≥ 50%, 124 of whom had detectable NTBI (≥0.47 µM, 1.81 µM [0.92-2.46 µM]) with a median serum ferritin 320 µg/L (226-442 µg/L). Ninety of 219 homozygotes had TS ≥ 75%, and all had detectable NTBI (2.21 µM [1.53-2.59 µM] with a median ferritin 338 µg/L [230-447 µg/L]). Of 125 homozygotes who last had phlebotomy ≥12 months ago (42 months [25-74 months], 92 had TS levels ≥ 50%, and 70 of these had NTBI ≥ 0.47 µM (2.06 µM [1.23-2.61µM]). Twenty-six of these 70 had a normal ferritin. Fifty-five of 125 had TS ≥ 75%, and NTBI was detected in all of these (2.32 µM [1.57-2.77 µM]) with a median ferritin 344 µg/L (255-418 µg/L). Eighteen of these 55 had a normal ferritin. In summary, NTBI is frequently found in C282Y homozygotes with TS ≥ 50%. Furthermore, C282Y homozygotes in the maintenance phase often have TS ≥ 50% together with a normal ferritin. Therefore, monitoring the TS level during the maintenance phase is recommended as an accessible clinical marker of the presence of NTBI.