Donor age is the major determinant of low-level blood lead burden in the REDS recalled donor cohort

Abstract

BACKGROUND: Donated blood is a biological product whose molecular composition is influenced by donor exposures, including environmental toxicants such as heavy metals. Among these, lead is particularly relevant because no exposure level is considered completely without risk. Most circulating lead partitions into red blood cells (RBCs), and transfused RBC units can increase blood lead levels in vulnerable recipients. Whether donor lead burden reflects donor biology and associates with storage phenotypes remains unclear.

STUDY DESIGN AND METHODS: We analyzed 638 donors from the REDS donor study. Lead was measured by inductively-coupled plasma mass spectrometry and linked to donor demographics, donation frequency, end-of-storage hemolysis phenotypes, and RBC multi-omics features. Multi-omics associations were assessed by Spearman correlation and repeated using partial Spearman correlations adjusted for donor age, with false-discovery-rate correction across all tested features.

RESULTS: Lead levels ranged from 0.14 to 8.56 μg/dL. Donor age was the dominant correlate of lead (rho = 0.51, p < 1 × 10-4), whereas BMI showed only a weak inverse association, despite its positive relationship with age in the cohort. Lead did not differ by sex, and frequent donation (>9 donations in the prior 24 months) was not associated with lower lead levels. At day 42, lead associated with 53 and 5 of 3468 multi-omics features in unadjusted and adjusted analyses, respectively.

CONCLUSION: Low-level donor lead burden is strongly age-dependent. These findings identify donor age as a major determinant of the RBC lead exposome and highlight candidate age-independent features for further mechanistic study.