The benefits of iron supplementation following blood donation vary with baseline iron status

Abstract

Whole blood donation rapidly removes approximately 10% of a donor's blood volume and stimulates substantial changes in iron metabolism and erythropoiesis. We sought to identify donors who benefit from iron supplementation, describe the nature of the benefit, and define the time course for recovery from donation. Blood samples were collected over 24 weeks following whole blood donation from 193 participants, with 96 participants randomized to 37.5 mg daily oral iron. Changes in total body, red blood cell (RBC), and storage iron, hepcidin, erythropoietin, and reticulocyte count were modeled using semiparametric curves in a mixed model. and the changes were compared among six groups defined by baseline ferritin (<12; 12-50; ≥50 ng/mL) and iron supplementation. The effect of oral iron on storage and RBC iron recovery was minimal in donors with baseline ferritin ≥50 ng/mL, but sizeable when ferritin was <50 ng/mL. Iron initially absorbed went to RBC and storage iron pools when ferritin was <12 ng/mL but went mostly to RBCs when ferritin was ≥12 ng/mL. Donors with ferritin ≥12 ng/mL had a "ripple" increase in reticulocytes ~100 days after donation indicating physiological responses occur months following donation. Thus, iron supplements markedly enhance recovery from whole blood donation in donors with ferritin <50 ng/mL. However, full recovery from donation requires over 100 days when taking iron. The findings also highlight the value of the study of blood donors for understanding human hemoglobin and iron metabolism and their usefulness for future studies as additional biomarkers are discovered.

Trial registration: ClinicalTrials.gov NCT01555060.

FIGURE 1

Iron supplements enhance recovery of TBI and RBC iron following whole blood donation when baseline ferritin is < 50 ng/mL and degree and duration of storage iron deficiency following whole blood donation. A, Change in TBI following whole blood donation. Curves were analyzed for baseline, baseline shift at 24 weeks, maximum decrease from baseline, maximum rate of increase, and time of minimum. B, Change in RBC iron following whole blood donation. Curves were analyzed for baseline, baseline shift at 24 weeks, and maximal rate of increase. C, Change in storage iron following whole blood donation. Curves were analyzed for baseline, baseline shift at 24 weeks, maximal decrease from baseline, maximal rate of increase, and time of minimum. Red lines are donors who took 37.5 mg daily oral iron. Blue lines are donors who did not take iron

FIGURE 2

Iron supplements accelerate hepcidin recovery when ferritin is ≥12, but not < 12 ng/mL. Change in hepcidin following whole blood donation. Curves were analyzed for baseline, baseline shift at 24 weeks, maximum decrease from baseline, maximum rate of increase, and time of minimum. Red line is donors who took 37.5 mg daily oral iron. Blue line is donors who did not take iron

FIGURE 3

Iron supplements decrease the duration of elevated erythropoietin following whole blood donation when baseline ferritin is < 50 ng/mL. Change in erythropoietin following whole blood donation. Curves were analyzed for baseline, baseline shift at 24 weeks, maximum increase, and maximum rate of decrease after day14. Red line is donors who took 37.5 mg daily oral iron. Blue line is donors who did not take iron

FIGURE 4

Iron supplements prolonged the post-whole blood donation elevation in reticulocyte count. Change in reticulocyte count following whole blood donation. Curves were analyzed for baseline, time of initial maximum, and maximum initial increase. Red line is donors who took 37.5 mg daily oral iron. Blue line is donors who did not take iron