Elevated risk for iron depletion in high-school age blood donors

Abstract

Background: High school students 16 to 18 years-old contribute 10% of the US blood supply. Mitigating iron depletion in these donors is important because they continue to undergo physical and neurocognitive development.

Study design and methods: Study objectives were to determine the prevalence of iron depletion in 16- to 18-year-old donors and whether their risk for iron depletion was greater than adult donors. Successful, age-eligible donors were enrolled from high school blood drives at two large US blood centers. Plasma ferritin testing was performed with ferritin less than 12 ng/mL as our primary measure of iron depletion and ferritin less than 26 ng/mL a secondary measure. Multivariable repeated-measures logistic regression models evaluated the role of age and other demographic/donation factors.

Results: Ferritin was measured from 4265 enrollment donations September to November 2015 and 1954 follow-up donations through May 2016. At enrollment, prevalence of ferritin less than 12 ng/mL in teenagers was 1% in males and 18% in females making their first blood donation, and 8% in males and 33% in females with prior donations. Adjusted odds for ferritin less than 12 ng/mL were 2.1 to 2.8 times greater in 16- to 18-year-olds than in 19- to 49-year-olds, and for ferritin less than 26 ng/mL were 3.3- to 4.7-fold higher in 16- to 18-year-olds. Progression to hemoglobin deferral was twice as likely in 16- to 18-year-old versus 19- to 49-year-old females.

Conclusion: Age 16 to 18 years-old is an independent risk factor for iron deficiency in blood donors at any donation frequency. Blood centers should implement alternate eligibility criteria or additional safety measures to protect teenage donors from iron depletion.

Figure 1:. CHILL study flow diagram.

Number of eligible donors by age (years completed) and sex at enrollment, with total donation count during CHILL (where “Nx” represents N successful donation procedures with 1 or 2 red cell units donated per procedure). Ferritin values were available from all 4,265 enrollment donations and from 1,954 of 2,290 follow-up donations.

Figure 2:. Hemoglobin and ferritin values at enrollment.

A) Mean hemoglobin (± 1SD) of first-time (FT) and repeat (RPT) donors at enrollment stratified by age and sex (○ females, ● males). B) Median ferritin (IQR) of FT and RPT donors at enrollment stratified by age and sex, plotted on log 2 scale (○ females, ● males). C) Prevalence of ferritin <12 ng/mL (light blue) and <26 ng/mL (dark blue) among FT and RPT female donors at enrollment stratified by age. D) Prevalence of ferritin <12 ng/mL (light blue) and <26 ng/mL (dark blue) among FT and RPT male donors at enrollment stratified by age.

Figure 2:. Hemoglobin and ferritin values at enrollment.

A) Mean hemoglobin (± 1SD) of first-time (FT) and repeat (RPT) donors at enrollment stratified by age and sex (○ females, ● males). B) Median ferritin (IQR) of FT and RPT donors at enrollment stratified by age and sex, plotted on log 2 scale (○ females, ● males). C) Prevalence of ferritin <12 ng/mL (light blue) and <26 ng/mL (dark blue) among FT and RPT female donors at enrollment stratified by age. D) Prevalence of ferritin <12 ng/mL (light blue) and <26 ng/mL (dark blue) among FT and RPT male donors at enrollment stratified by age.

Figure 3:. Mean ferritin at enrollment in CHILL first-time donors vs NHANES subjects from 2001–2002.

Mean and 95% C.I. of the mean ferritin for CHILL first time donors at enrollment are plotted alongside age-sex counterparts from NHANES 2001–2002. Red denotes female values; blue denotes male values.

Figure 4:. Prevalence of and risk for ferritin <12 ng/mL or <26 ng/mL across 6219 study visits.

A) Unadjusted odds ratios for ferritin <12 ng/mL (left) and <26 ng/mL (right). Reference for Age is 19–49; for Sex is male; for Weight is ≥200 pounds; for Interval Since Last Donation is ≥52 weeks; for 24-Month Donation Frequency is 0. “n” represents the number of donations from subjects at each level of the modeled covariates, and “% <12” and “% <26” represent the proportion of donations at each level below the respective ferritin cutoff. B) Adjusted odds ratios for ferritin <12 ng/mL (left) and <26 ng/mL (right) in repeated measures multivariable logistic regression. Reference group is 19–49 yo male with 0 RBC donations in 24 months and weight ≥200 pounds; prevalence of ferritin <12 ng/mL is 0% and <26 ng/mL is 2%. Double red blood cell donation as most recent phlebotomy and blood center were also included in both models, but were not statistically significant and are not shown.

Figure 4:. Prevalence of and risk for ferritin <12 ng/mL or <26 ng/mL across 6219 study visits.

A) Unadjusted odds ratios for ferritin <12 ng/mL (left) and <26 ng/mL (right). Reference for Age is 19–49; for Sex is male; for Weight is ≥200 pounds; for Interval Since Last Donation is ≥52 weeks; for 24-Month Donation Frequency is 0. “n” represents the number of donations from subjects at each level of the modeled covariates, and “% <12” and “% <26” represent the proportion of donations at each level below the respective ferritin cutoff. B) Adjusted odds ratios for ferritin <12 ng/mL (left) and <26 ng/mL (right) in repeated measures multivariable logistic regression. Reference group is 19–49 yo male with 0 RBC donations in 24 months and weight ≥200 pounds; prevalence of ferritin <12 ng/mL is 0% and <26 ng/mL is 2%. Double red blood cell donation as most recent phlebotomy and blood center were also included in both models, but were not statistically significant and are not shown.

Figure 5:. The impact of donation frequency on iron status is mediated by sex and by age.

In separate longitudinal regression models, interaction terms indicate that the increase in risk for low ferritin with increasing donation frequency varies by sex (A, B) and by age (C, D). 5A plots the predicted prevalence (± 1 SE) of ferritin <12 ng/mL by sex and RBC units donated in 24 months if all 6,219 donation visits were made by subjects of the indicated sex, assuming all other covariate distributions were unchanged (solid line = females, dashed line = males). 5B plots expected prevalence of ferritin <26 ng/mL for the sex by donation frequency interaction. A separate model with an interaction term for age group (16–18 vs 19–49 years old) and donation frequency shows that donors 16 to 18 yo are more likely to have ferritin <12 ng/mL (C) and <26 ng/mL (D) with no donations and that the gap between younger and older donors grows with successive donations (solid line = 19–49 yo, dashed line = 16–18 yo).