Validity of donor-reported iron supplementation practices obtained at the time of donation.

BACKGROUND: Iron supplementation (IS) improves blood donors' iron stores and allows more frequent blood donation. Understanding the accuracy of self-reported IS is helpful for potential application of IS practices to donor eligibility or donation intervals. METHODS: Successful whole blood and red cell apheresis donors completed a survey at donation on the use of select dietary supplements. Respondents reporting use of either iron pills (IP) or multivitamins (MV) were invited by email to complete a similar follow-up survey 6-8 weeks later and to provide the quantitative iron content of IS by referring the donor to the pill bottle label. Consistency between baseline and follow-up responses was assessed overall and by pill type and demographic variables. RESULTS: Of 2444 donors answering the baseline survey, 40% (978) reported MV or IP at donation, 354 of whom completed the follow-up survey. A majority of survey respondents (56%-61%) reported taking iron across the two surveys, and 21%-24% took MV but were uncertain if their pills contained iron. Of 215 reporting IS at baseline, overall concordance at follow-up was 68% and was higher for donors who were female, ≥50-years old, and taking iron as an iron pill rather than in a multivitamin. CONCLUSION: Consistency of donor responses may be insufficient for use in guiding donor eligibility. Referring donors to their pill bottles was unsuccessful in improving the high frequency of uncertain responses. Incorporating IS into donor eligibility determinations is a complex endeavor that will benefit from careful planning and from post-implementation monitoring.

Iron status and self-reported fatigue in blood donors.

Fatigue is a reported symptom of iron depletion, but studies in blood donors show no conclusive link. We conducted an observational analysis of data from the STRIDE randomized trial to evaluate association of iron status with self-reported fatigue. STUDY DESIGN AND METHODS: Three blood centers randomly assigned 692 frequent donors to education or iron supplementation treatments. Biomarkers for iron status were measured during 20 to 24 months of follow-up. A fatigue score was derived from an 11-item questionnaire at baseline and final visits, and associations between iron status and fatigue were assessed. RESULTS: Final lab and questionnaire data were evaluable from 337 subjects. At baseline, female sex, older age, and anemia were associated with fatigue, but iron status was not. Mean (±SD) fatigue score change was 0.0 (±0.5). Mean (±SD) increase in iron stores was 1.0 (±3.5) mg/kg, but changes in body iron stores were not associated with fatigue score changes (0.01 per mg/kg; 95% CI, -0.01 to 0.02) or with fatigue (RR, 1.01; 95% CI, 0.99 to 1.04). The only factor associated with fatigue score changes was baseline fatigue (0.36; 95% CI, 0.25 to 0.48). CONCLUSION: Among high-frequency donors, neither iron status at baseline nor changes in iron status predicted fatigue during follow-up, with improvements limited to those with higher levels of baseline fatigue. Assessment of the association between iron and fatigue in blood donors benefits from careful consideration of study design and the study population.

Association of proton pump inhibitor and histamine H2-receptor antagonists with restless legs syndrome.

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge-Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H2A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13-1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03-1.95; p = 0.03) and H2A (OR = 1.56; CI, 1.10-2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H2As (OR = 1.29; CI, 1.20-1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17-1.38; p < 0.001), but not H2As alone (OR = 1.18; CI, 0.92-1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H2A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H2A in populations at particular risk for RLS.

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

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.

Genetic and behavioral modification of hemoglobin and iron status among first-time and high-intensity blood donors.

BACKGROUND: Some people rapidly develop iron deficiency anemia following blood donation, while others can repeatedly donate without becoming anemic. METHODS: Two cohorts of blood donors were studied. Participants (775) selected from a 2-year longitudinal study were classified into six analysis groups based on sex, donation intensity, and low hemoglobin deferral. Associations with iron supplement use, cigarette smoking, and four genetic variants of iron metabolism were examined at enrollment and with longitudinal regression models. An unbiased assessment of genetic variability and ability to repeatedly donate blood without experiencing low hemoglobin deferral was conducted on participants (13,403) in a cross-sectional study who were examined by genome wide association (GWA). RESULTS: Behaviors and genetic variants were associated with differences in hemoglobin and ferritin change following repeated donation. At least weekly iron supplement use was associated with improved status in first-time donors, while daily use was associated with improved status in high-intensity donors. Cigarette smoking was associated with 0.5 g/dL increased hemoglobin in high-intensity donors. A736V in TMPRSS6 was associated with a rapid drop in hemoglobin and ferritin in first-time females following repeated donation. Conversely, the protective TMPRSS6 genotype was not enriched among high-intensity donors. H63D in HFE was associated with increased hemoglobin in female high-intensity donors. However, no differences in genotype between first-time and high-intensity donors were found in GWA analyses. CONCLUSION: Behavioral and genetic modifiers contributed to first-time donor hemoglobin and iron status, while iron supplement use was more important than underlying genetics in high-intensity donors.

Prevalence, risk factors, and ferritin testing to mitigate iron depletion in male plateletpheresis donors.

BACKGROUND: Most single-donor platelet (SDP) donors transition to plateletpheresis after prior red blood cell (RBC) donation. Recruitment may follow identification of a high platelet count, a marker associated with iron depletion (ID). SDP donors may have underrecognized risk for iron depletion. STUDY DESIGN AND METHODS: To assess the prevalence of ID, we performed ferritin testing on male plateletpheresis donors with hemoglobin levels less than 13.5 g/dL. Multivariable logistic regression identified risk factors for low ferritin (LF; ferritin ≤26 ng/mL) and absent iron stores (AIS; ferritin <12 ng/mL). To assess the impact of notifying donors of LF results, we compared donation behavior of "Test" subjects before and after sending an LF notification letter to that of "Control" subjects before and after increasing the minimum hemoglobin for male donors. An electronic survey to Test donors inquired about iron supplementation practices. RESULTS: Prevalence of LF was 50% and AIS was 23%, with increase in risk associated with more frequent SDP donation, both controlling for RBC donation and in donors with no recent RBC donations. Donation frequency after intervention declined less in 1272 Test donors (19%, from 13.9 to 11.2 annualized donations) than in 878 Control donors (49%, from 12.3 to 6.3 donations). Only 20% of Test donors reported taking supplemental iron when they received the LF letter; 64% of those not taking iron initiated iron supplementation following the letter. CONCLUSIONS: Donors were responsive to notification of LF and attendant messaging on iron supplementation. Ferritin testing potentially benefits donor health and a stable platelet supply.

Iron status and risk factors for iron depletion in a racially/ethnically diverse blood donor population.

BACKGROUND: The optimal approach for reducing iron depletion (ID) in blood donors may vary depending on biologic or behavioral differences across donors. STUDY DESIGN AND METHODS: More than 12,600 successful whole blood donors were enrolled from four US blood centers for ferritin testing. The study population was enriched for racial/ethnic minorities (1605 African American, 1616 Asian, 1023 Hispanic). Subjects completed questionnaires on ID risk factors. Logistic regression identified predictors of absent iron stores (AIS; ferritin <12 ng/mL) and low ferritin (LF; ferritin <26 ng/mL). RESULTS: Across all subjects, 19% had AIS and 42% had LF, with a sharp increase in risk observed with increasing donation intensity and among women a large decrease in risk in those more than 50 years old. When other factors were controlled for, African American and Asian donors showed 20% to 25% decreased risk for AIS compared to non-Hispanic Caucasian donors, while Hispanic donors had 25% higher risk. Daily iron supplementation reduced risk for LF and AIS by 30% to 40%, respectively, while the benefit from less frequent use was lower (7%-19% protection). Regular antacid use was associated with at least 20% increment to risk. Use of oral contraceptives or estrogen in females reduced risk by 16% to 22%, while males who reported supplemental testosterone use had a 50% to 125% greater risk for LF and AIS. CONCLUSIONS: This study confirms high prevalence of LF and AIS in US donors and the principal risk factors of age, sex, and donation frequency. Additional demographic and behavioral risk factors of secondary importance might allow for refinement of ID mitigation strategies.

Iron supplementation by blood donors: demographics, patterns of use, and motivation.

BACKGROUND: Iron supplements reduce the risk of iron depletion in blood donors. Recent initiatives have sought to increase use of donor iron supplementation (IS), but a baseline description of blood donor supplement practices is needed. STUDY DESIGN AND METHODS: Presenting blood donors received a questionnaire inquiring about IS beginning in December 2015. Responses were linked to operational donor information and analyzed by multivariable statistics. RESULTS: During the first 6 months, 53,989 evaluable responses were obtained from 80% of presenting donors. Overall, donors of 21.4% of units reported taking iron as a multivitamin (14.6%), in a separate iron supplement (4.1%), or both (2.6%). IS use was associated with female sex (27% vs. 16% in males), increasing age (30% of donors 60+ vs. 8% in 17- to 25-year-olds), and more frequent previous donations (33% in those with 6+ units donated vs. 7% in first-time donors). Multivariable logistic regression models stratified by sex indicated that donation frequency was most strongly associated with IS in females, and age most strongly associated with IS in males. Motivation for IS varied by type, with more than 75% of donors taking multivitamins with iron naming "General health and wellness," while donors taking a separate iron supplement predominantly listed motivations related to blood donation. CONCLUSIONS: A strong majority of blood donors report not using supplemental iron. Most donors with IS used multivitamins with iron and listed support of general health rather than blood donation as their motivation for taking iron. Effective communication of the importance of iron for blood donation is needed.

Blood Utilization and Transfusion Reactions in Pediatric Patients Transfused with Conventional or Pathogen Reduced Platelets.

OBJECTIVES: To assess the safety and efficacy of a Food and Drug Administration-approved pathogen-reduced platelet (PLT) product in children, as ongoing questions regarding their use in this population remain. STUDY DESIGN: We report findings from a quality assurance review of PLT utilization, associated red blood cell transfusion trends, and short-term safety of conventional vs pathogen-reduced PLTs over a 21-month period while transitioning from conventional to pathogen-reduced PLTs at a large, tertiary care hospital. We assessed utilization in neonatal intensive care unit (NICU) patients, infants 0-1 year not in the NICU, and children age 1-18 years (PED). RESULTS: In the 48 hours after an index conventional or pathogen-reduced platelet transfusion, respectively, NICU patients received 1.0 ± 1.4 (n = 91 transfusions) compared with 1.2 ± 1.3 (n = 145) additional platelet doses (P = .29); infants 0-1 year not in the NICU received 2.8 ± 3.0 (n = 125) vs 2.6 ± 2.6 (n = 254) additional platelet doses (P = .57); and PEDs received 0.9 ± 1.6 (n = 644) vs 1.4 ± 2.2 (n = 673) additional doses (P < .001). Time to subsequent transfusion and red cell utilization were similar in every group (P > .05). The number and type of transfusion reactions did not significantly vary based on PLT type and no rashes were reported in NICU patients receiving phototherapy and pathogen-reduced PLTs. CONCLUSIONS: Conventional and pathogen-reduced PLTs had similar utilization patterns in our pediatric populations. A small, but statistically significant, increase in transfusions was noted following pathogen-reduced PLT transfusion in PED patients, but not in other groups. Red cell utilization and transfusion reactions were similar for both products in all age groups.

Frequent blood donations alter susceptibility of red blood cells to storage- and stress-induced hemolysis.

BACKGROUND: Frequent whole blood donations increase the prevalence of iron depletion in blood donors, which may subsequently interfere with normal erythropoiesis. The purpose of this study was to evaluate the associations between donation frequency and red blood cell (RBC) storage stability in a racially/ethnically diverse population of blood donors. STUDY DESIGN: Leukoreduced RBC concentrate-derived samples from 13,403 donors were stored for 39 to 42 days (1-6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Iron status was evaluated by plasma ferritin measurement and self-reported intake of iron supplements. Donation history in the prior 2 years was obtained for each subject. RESULTS: Frequent blood donors enrolled in this study were likely to be white, male, and of older age (56.1 ± 5.0 years). Prior donation intensity was negatively associated with oxidative hemolysis (p < 0.0001) in multivariate analyses correcting for age, sex, and race/ethnicity. Increased plasma ferritin concentration was associated with increased RBC susceptibility to each of the three measures of hemolysis (p < 0.0001 for all), whereas self-reported iron intake was associated with reduced susceptibility to osmotic and oxidative hemolysis (p < 0.0001 for both). CONCLUSIONS: Frequent blood donations may alter the quality of blood components by modulating RBC predisposition to hemolysis. RBCs collected from frequent donors with low ferritin have altered susceptibility to hemolysis. Thus, frequent donation and associated iron loss may alter the quality of stored RBC components collected from iron-deficient donors. Further investigation is necessary to assess posttransfusion safety and efficacy in patients receiving these RBC products.

Blood, sweat, and tears: Red Blood Cell-Omics study objectives, design, and recruitment activities.

BACKGROUND: The Red Blood Cell (RBC)-Omics study was initiated to build a large data set containing behavioral, genetic, and biochemical characteristics of blood donors with linkage to outcomes of the patients transfused with their donated RBCs. STUDY DESIGN AND METHODS: The cohort was recruited from four US blood centers. Demographic and donation data were obtained from center records. A questionnaire to assess pica, restless leg syndrome, iron supplementation, hormone use, and menstrual and pregnancy history was completed at enrollment. Blood was obtained for a complete blood count, DNA, and ferritin testing. A leukocyte-reduced RBC sample was transferred to a custom storage bag for hemolysis testing at Storage Days 39 to 42. A subset was recalled to evaluate the kinetics and stability of hemolysis measures. RESULTS: A total of 13,403 racially/ethnically diverse (12% African American, 12% Asian, 8% Hispanic, 64% white, and 5% multiracial/other) donors of both sexes were enrolled and ranged from 18 to 90 years of age; 15% were high-intensity donors (nine or more donations in the prior 24 mo without low hemoglobin deferral). Data elements are available for 97% to 99% of the cohort. CONCLUSIONS: The cohort provides demographic, behavioral, biochemical, and genetic data for a broad range of blood donor studies related to iron metabolism, adverse consequences of iron deficiency, and differential hemolysis (including oxidative and osmotic stress perturbations) during RBC storage. Linkage to recipient outcomes may permit analysis of how donor characteristics affect transfusion efficacy. Repository DNA, plasma, and RBC samples should expand the usefulness of the current data set.

The operational implications of donor behaviors following enrollment in STRIDE (Strategies to Reduce Iron Deficiency in blood donors).

BACKGROUND: Donor behaviors in STRIDE (Strategies to Reduce Iron Deficiency), a trial to reduce iron deficiency, were examined. STUDY DESIGN AND METHODS: Six hundred ninety-two frequent donors were randomized to receive either 19 or 38 mg iron for 60 days or an educational letter based on their predonation ferritin. Compliance with assigned pills, response to written recommendations, change in donation frequency, and future willingness to take iron supplements were examined. RESULTS: Donors who were randomized to receive iron pills had increased red blood cell donations and decreased hemoglobin deferrals compared with controls or with pre-STRIDE donations. Donors who were randomized to receive educational letters had fewer hemoglobin deferrals compared with controls. Of those who received a letter advising of low ferritin levels with recommendations to take iron supplements or delay future donations, 57% reported that they initiated iron supplementation, which was five times as many as those who received letters lacking a specific recommendation. The proportion reporting delayed donation was not statistically different (32% vs. 20%). Of donors who were assigned pills, 58% reported taking them "frequently," and forgetting was the primary reason for non-compliance. Approximately 80% of participants indicated that they would take iron supplements if provided by the center. CONCLUSIONS: Donors who were assigned iron pills had acceptable compliance, producing increased red blood cell donations and decreased low hemoglobin deferrals compared with controls or with pre-STRIDE rates. The majority of donors assigned to an educational letter took action after receiving a low ferritin result, with more donors choosing to take iron than delay donation. Providing donors with information on iron status with personalized recommendations was an effective alternative to directly providing iron supplements.

Estimates of total body iron indicate 19 mg and 38 mg oral iron are equivalent for the mitigation of iron deficiency in individuals experiencing repeated phlebotomy.

Iron deficiency anemia is a common clinical condition often treated with tablets containing 65 mg of elemental iron. Such doses can elicit gastrointestinal side effects lowering patient compliance. Oral iron supplements also increase hepcidin production causing decreased fractional absorption of subsequent doses. Frequent blood donors often become iron deficient. Therefore, they were enrolled in a two-year study involving continued blood donations and randomization to receive no pill, placebo, 19, or 38 mg ferrous gluconate for 60 days. Total body iron (TBI) did not change for the subset of donors in the no pill and placebo groups who completed both enrollment and final visits (P = .21 and P = .28, respectively). However, repeated measures regression analysis on the complete dataset estimated a significant decrease in TBI of 52 mg/year for the placebo and no pill groups (P = .001). The effects of 19 and 38 mg iron supplementation on TBI were indistinguishable (P = .54). TBI increased by 229 mg after the initial 60 days of iron supplementation (P < .0001) and was maintained at this higher level with continued iron supplementation following each subsequent donation. The TBI increase was apportioned 51 mg to red cell iron (P < .0001) and 174 mg to storage iron (P < .0001). Changes in storage iron were negatively impacted by 57 mg due to concurrent antacid use (P = .04). These findings in blood donors suggest that much lower doses of iron than are currently used will be effective for clinical treatment of iron deficiency anemia.

Qualitative assessment of pica experienced by frequent blood donors.

BACKGROUND: Pica, the compulsive consumption of ice or other nonnutritious substances, is associated with iron deficiency, a common negative consequence of frequent blood donation. Because of this, blood donors, such as those participating in the Strategies to Reduce Iron Deficiency (STRIDE) study, are an ideal population to explore pica and iron deficiency. STUDY DESIGN AND METHODS: STRIDE was a 2-year intervention trial to assess the effectiveness of iron supplementation for mitigating iron deficiency in frequent blood donors. Subjects completed baseline and follow-up questionnaires that included questions about pica symptoms. In-depth telephone interviews were conducted with 14 of these subjects reporting pica symptoms and eight presumed controls (casual ice chewers) to gain a deeper understanding of pica symptoms and their impact on daily life and to make a final determination on the presence of pica. RESULTS: Pica was confirmed in five of the 14 subjects reporting symptoms and in two of eight controls. Outcome misclassification based on the questionnaire was attributed to inadequate assessment of several pica symptoms identified during the interview. Comparison of subjects' repeated quantitative iron measurements taken throughout STRIDE with subjects' final adjudicated pica status revealed a positive relationship between development of pica and worsening iron status; the opposite was found in those whose pica symptoms resolved. CONCLUSION: Continued refinement of pica symptom questions will allow for rapid and accurate detection of pica in frequent blood donors and confirmation of successful treatment with iron supplements.

Effect of iron supplementation on iron stores and total body iron after whole blood donation.

BACKGROUND: Understanding the effect of blood donation and iron supplementation on iron balance will inform strategies to manage donor iron status. STUDY DESIGN AND METHODS: A total of 215 donors were randomized to receive ferrous gluconate daily (37.5 mg iron) or no iron for 24 weeks after blood donation. Iron stores were assessed using ferritin and soluble transferrin receptor. Hemoglobin (Hb) iron was calculated from total body Hb. Total body iron (TBI) was estimated by summing iron stores and Hb iron. RESULTS: At 24 weeks, TBI in donors taking iron increased by 281.0 mg (95% confidence interval [CI], 223.4-338.6 mg) compared to before donation, while TBI in donors not on iron decreased by 74.1 mg (95% CI, -112.3 to -35.9; p < 0.0001, iron vs. no iron). TBI increased rapidly after blood donation with iron supplementation, especially in iron-depleted donors. Supplementation increased TBI compared to controls during the first 8 weeks after donation: 367.8 mg (95% CI, 293.5-442.1) versus -24.1 mg (95% CI, -82.5 to 34.3) for donors with a baseline ferritin level of not more than 26 ng/mL and 167.8 mg (95% CI, 116.5-219.2) versus -68.1 mg (95% CI, -136.7 to 0.5) for donors with a baseline ferritin level of more than 26 ng/mL. A total of 88% of the benefit of iron supplementation occurred during the first 8 weeks after blood donation. CONCLUSION: Donors on iron supplementation replaced donated iron while donors not on iron did not. Eight weeks of iron supplementation provided nearly all of the measured improvement in TBI. Daily iron supplementation after blood donation allows blood donors to recover the iron loss from blood donation and prevents sustained iron deficiency.

Potential impact on blood availability and donor iron status of changes to donor hemoglobin cutoff and interdonation intervals.

BACKGROUND: A minimum male hemoglobin (Hb) level of 13.0 g/dL becomes a Food and Drug Administration requirement effective May 2016. In addition, extending whole blood (WB) interdonation intervals (IDIs) beyond 8 weeks has been considered to reduce iron depletion in repeat blood donors. This study estimates the impact these changes might have on blood availability and donor iron status. STUDY DESIGN AND METHODS: Six blood centers participating in Retrovirus Epidemiology Donor Study-II (REDS-II) collected information on all donation visits from 2006 to 2009. Simulations were developed from these data using a multistage approach that first sought to adequately reproduce the patterns of donor return, Hb and ferritin levels, and outcomes of a donor's visit (successful single- or double-red blood cell donation, deferral for low Hb) observed in REDS-II data sets. Modified simulations were used to predict the potential impact on the blood supply and donor iron status under different Hb cutoff and IDI qualification criteria. RESULTS: More than 10% of WB donations might require replacement under many simulated scenarios. Longer IDIs would reduce the proportion of donors with iron depletion, but 80% of these donors may remain iron-depleted if minimal IDIs increased to 12 or 16 weeks. CONCLUSION: Higher Hb cutoffs and longer IDIs are predicted to have a potentially large impact on collections but only a modest impact on donor iron depletion. Efforts to address iron depletion should be targeted to at-risk donors, such as iron supplementation programs for frequent donors, and policy makers should try to avoid broadly restrictive donation requirements that could substantially reduce blood availability.

A randomized, blinded, placebo-controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors.

BACKGROUND: The historical approach of offering dietary advice to donors with low hemoglobin (Hb) is ineffective for preventing iron deficiency in frequent donors. Alternative approaches to maintaining donor iron status were explored. STUDY DESIGN AND METHODS: Frequent blood donors were randomly assigned into five arms for 2 years of follow-up. Three double-blinded arms provided 60 once-daily pills after each donation (38, 19, or 0 mg of iron). Two single-blinded arms provided iron status (ferritin) or no information letters after each donation. Ferritin, soluble transferrin receptor, and complete blood count were measured at each donation. RESULTS: There were 692 subjects enrolled and 393 completed the study. Subjects in pill groups deenrolled more than those in letter groups (39% vs. 7%). Adverse events occurred equally in subjects receiving iron or placebo pills. Of those completing the study, the prevalence of ferritin of less than 12 or less than 26 ng/mL declined by more than 50% and was statistically indistinguishable in the three intervention groups (19 or 38 mg of iron; iron status letter). Longitudinal analyses of all subjects showed improved iron status in iron pill groups and worsening iron status in control groups (placebo; no information letter). The iron pill groups experienced a net increase of approximately 0.6 g/dL Hb compared to control groups. The iron status letter group had little change in Hb. CONCLUSION: Providing 19 or 38 mg of daily iron or iron status information were effective and mostly equivalent interventions for mitigating iron deficiency in regular donors when compared at the end of the 2-year longitudinal phase of the study. Donors without intervention had worsened iron deficiency with continued donation.

Oral iron supplementation after blood donation: a randomized clinical trial.

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.

Blood donor iron status: are we bleeding them dry?

PURPOSE OF REVIEW: This review examines the recent research on the prevalence, determinants and importance of low iron in blood donors, and on the efforts to reduce or prevent iron depletion in donor populations. RECENT FINDINGS: Female donors, especially younger women, are at highest risk for donation-induced low iron, but menopausal women and high-frequency donors of both sexes also face considerable risk for iron depletion. Predonation screening for hemoglobin contributes little information on donor iron status. Consumption of supplemental iron is helpful in preventing or reversing low iron, and waiting longer between donations also facilitates the recovery of the iron lost through donation. SUMMARY: Although the impact of phlebotomy-related iron depletion on donor health requires better documentation, measures are available now that can be deployed on a targeted or standardized basis. Blood centers, regulators, and donors should continue to evaluate different approaches for addressing this problem, with the likely outcome that no single measure is optimal for maintaining adequate collections while safeguarding donor health.