Demographic Patterns and Transfusion Implications of Foetal Haemoglobin (HbF) in Blood Donors in England

Abstract

Background Foetal haemoglobin (HbF) normally declines to <1 % in healthy adults, but persistence can complicate haemoglobinopathy screening, neonatal transfusion, and laboratory interpretation. In the United Kingdom (UK), the adult threshold of <1 % was derived from predominantly White cohorts using pre-high-performance liquid chromatography (HPLC). Contemporary donor-based data are limited, and the relevance of this cut-off in a diverse donor base is uncertain. Aim To estimate the prevalence of elevated HbF (>1 %) in a current National Health Service Blood and Transplant (NHSBT) donor cohort and assess demographic associations with sex, ethnicity, and age. Methods A retrospective cross-sectional study analysed 579 anonymised donations processed at NHSBT Filton in June 2025. HbF was quantified on a Tosoh HLC 723 G8 HPLC platform (limit of quantification 0.1 %, coefficient of variation (CV) < 2 %). Prespecified non-parametric analyses included Mann-Whitney U (sex), Kruskal-Wallis H (ethnicity), and Rho-Spearman’s correlation coefficient (ρ) (age). Wilson and bootstrap methods generated 95 % confidence intervals for prevalence estimates. Results HbF ranged from 0.10 % to 2.90 % (median 0.50 %, interquartile range [IQR] 0.30-0.60 %). Twenty-nine donors (5.01 %) had HbF > 1.0 % (95 % confidence interval [CI]: 3.51-7.10, bootstrap CI: 3.28-6.91). Females had significantly higher HbF than males (p < 0.001, rank biserial correlation coefficient [r_rb] = 0.192). No significant differences were observed between White, Asian, and Black donors (p = 0.152), and HbF showed a weak inverse correlation with age (ρ = –0.083, p = 0.045). Conclusions One in twenty screened blood donors in this cohort had HbF > 1 %. These data suggest mild HbF elevations may be more common in contemporary donors than assumed. Larger, multi-centre studies with genetic and clinical follow-up are needed to determine whether sex- or context-specific thresholds improve diagnostic specificity without compromising haemoglobinopathy detection.