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.