Potential Health Consequences of Regular Blood Donation: Current Evidence and Remaining Uncertainties

Blood donation sustains an estimated 118 million annual donations worldwide, and while advances in infectious disease screening have greatly reduced recipient risk, the long-term health of repeat donors has received comparatively less attention. This cumulative review synthesises current evidence on the principal acquired complications of regular blood donation across all modalities-whole blood, plasmapheresis, and plateletpheresis-addressing iron deficiency, plasma protein depletion, apheresis-related lymphopenia, clonal haematopoiesis of indeterminate potential (CHIP), and micronutrient deficiency. Iron deficiency affects 15-36% of frequent whole blood donors and is systematically underdetected by haemoglobin-based screening alone; ferritin-guided interval adjustment and oral supplementation are effective countermeasures. Regular plasmapheresis depletes immunoglobulins (IgG below normal in 5-15% of high-frequency donors), albumin, and coagulation factors, compounded by cumulative citrate-mediated hypocalcaemia. Plateletpheresis causes measurable subset-selective T-cell and NK-cell depletion, with CD4⁺ counts below clinically significant thresholds in a minority of the most frequent donors, an observation of unknown significance. Emerging molecular data indicate that repeated haematopoietic stress selectively enriches low-risk, EPO-responsive DNMT3A clonal variants without increasing malignant risk. Regular blood donation if properly applied is a safe process. Across all domains, current eligibility criteria based on haemoglobin alone turn out to be inadequate; a shift to multiparameter, individualised and targeted donor monitoring-integrating ferritin, serum proteins, differential leucocyte counts, and micronutrient profiling-is both evidence-suggested and ethically worth considering to sustain the long-term health of voluntary donor populations.