Oral iron supplementation after blood donation: a randomized clinical trial

Abstract

Importance: Although blood donation is allowed every 8 weeks in the United States, recovery of hemoglobin to the currently accepted standard (12.5 g/dL) is frequently delayed, and some donors become anemic.

Objective: To determine the effect of oral iron supplementation on hemoglobin recovery time (days to recovery of 80% of hemoglobin removed) and recovery of iron stores in iron-depleted ("low ferritin," ≤26 ng/mL) and iron-replete ("higher ferritin," >26 ng/mL) blood donors.

Design, setting, and participants: Randomized, nonblinded clinical trial of blood donors stratified by ferritin level, sex, and age conducted in 4 regional blood centers in the United States in 2012. Included were 215 eligible participants aged 18 to 79 years who had not donated whole blood or red blood cells within 4 months.

Interventions: One tablet of ferrous gluconate (37.5 mg of elemental iron) daily or no iron for 24 weeks (168 days) after donating a unit of whole blood (500 mL).

Main outcomes and measures: Time to recovery of 80% of the postdonation decrease in hemoglobin and recovery of ferritin level to baseline as a measure of iron stores.

Results: The mean baseline hemoglobin levels were comparable in the iron and no-iron groups and declined from a mean (SD) of 13.4 (1.1) g/dL to 12.0 (1.2) g/dL after donation in the low-ferritin group and from 14.2 (1.1) g/dL to 12.9 (1.2) g/dL in the higher-ferritin group. Compared with participants who did not receive iron supplementation, those who received iron supplementation had shortened time to 80% hemoglobin recovery in both the low-ferritin (mean, 32 days, interquartile range [IQR], 30-34, vs 158 days, IQR, 126->168) and higher-ferritin groups (31 days, IQR, 29-33, vs 78 days, IQR, 66-95). Median time to recovery to baseline ferritin levels in the low-ferritin group taking iron was 21 days (IQR, 12-84). For participants not taking iron, recovery to baseline was longer than 168 days (IQR, 128->168). Median time to recovery to baseline in the higher-ferritin group taking iron was 107 days (IQR, 75-141), and for participants not taking iron, recovery to baseline was longer than 168 days (IQR, >168->168). Recovery of iron stores in all participants who received supplements took a median of 76 days (IQR, 20-126); for participants not taking iron, median recovery time was longer than 168 days (IQR, 147->168 days; P < .001). Without iron supplements, 67% of participants did not recover iron stores by 168 days.

Conclusions and relevance: Among blood donors with normal hemoglobin levels, low-dose iron supplementation, compared with no supplementation, reduced time to 80% recovery of the postdonation decrease in hemoglobin concentration in donors with low ferritin (≤26 ng/mL) or higher ferritin (>26 ng/mL).

Trial registration: clinicaltrials.gov Identifier: NCT01555060.

Figure 1. Hemoglobin and Iron Recovery Study (HEIRS) Flow Diagram

^aAll participants had data from ≥6 follow-up visits; 3 individuals had 6 visits, and 93 had 7 visits. ^bAll participants had data from ≥6 follow-up visits; 5 individuals had 6 visits, and 92 had 7 visits.

Figure 2. Time to Hemoglobin Recovery According to Treatment and Baseline Ferritin Level

A, Mean hemoglobin for each group vs time since donation. Time “0” is the day of donation. B, Hemoglobin expressed as a percentage of initial hemoglobin value. Hemoglobin recovery was significantly higher than baseline in the low-ferritin group (≤26 ng/mL) who took iron (mean, 106.0%; 95% CI, 104.3%–107.7%; P < .001) and significantly lower than baseline in the higher-ferritin group (>26 ng/mL) who took no iron (mean, 98.1%; 95% CI, 96.6%–99.6%; P = .02). Dotted line indicates 100% of initial hemoglobin value; error bars, 95% confidence intervals.

Figure 3. Mean Ferritin Level for Each Group vs Time Since Donation

After a donor gives 500 mL of whole blood, ferritin decreases by approximately 30 ng/mL over a 30-day period, as depicted in the no-iron, iron-replete group (open triangles). Each ng/mL of ferritin equates to 8 to 10 mg of storage iron; thus, 30 × 8 mg = 240 mg, approximately the amount of iron contained in each unit of blood. Reconstitution of storage iron was not observed until after recovery of hemoglobin, as indicated in the upward change in slope of the ferritin recovery curve in the no-iron, higher-ferritin group, at approximately day 84. Dotted line indicates 26 ng/mL, the value used to stratify iron-deficient and iron-replete donors at enrollment; error bars, 95% confidence intervals.

Figure 4. Mean Time to 80% Hemoglobin Recovery by Quartile of Ferritin and Treatment Assignment

The confidence intervals are censored at the end of follow-up at 168 days. No mean is shown for the lowest ferritin quartile for participants not taking iron because the mean was longer than 168 days.