Each whole blood donation stimulates erythropoiesis by 2.5% to 4% to replace lost cells. Since male blood donors can donate up to six times per year, increased levels of erythropoietin may represent a novel selection pressure on hematopoietic stem cells (HSCs). To determine if frequent, repeated whole blood donations favor certain mutations in HSCs or increase clonal hematopoiesis, researchers analyzed two age- and health-matched cohorts of males over 60 years of age. One cohort included 217 males with over 100 whole blood donations, while the other included 212 males with less than ten donations. No significant difference in the overall incidence of clonal hematopoiesis was found between the two cohorts. The most prevalent mutations were observed in the DNMT3A and TET2 genes, which are commonly affected in clonal hematopoiesis. Distinct patterns of genetic mutations, however, were observed in both cohorts. Based on CRISPR/Cas9 mutated human HSCs in cultures, mutations observed in frequent donors expand when exposed to erythropoietin but not inflammatory stimuli (unlike pre-leukemia mutations which expand when exposed to inflammatory stimuli). Further research is needed to assess the effects of frequent blood donation on HSCs.
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