Blood donation is crucial for modern medicine, providing vital products for a wide range of medical treatments. However, only a small percentage of eligible healthy individuals, approximately 4%, regularly donate blood. In North America and Europe, blood donation restrictions allow women to donate up to four times per year and men up to six times to prevent iron depletion. A single blood donation amounts to 10% of the donated blood relative to the total blood volume, but red blood cell production increases by 2.5% to 4% because of the reduction in blood volume.
Blood stem cell activation and multiplication occur through the donation process, but environmental factors such as infections or chemotherapy combined with additional factors like cytokines and blood loss may affect this process. Researchers have recently investigated how multiple blood donations affect the hereditary traits within blood stem cells. The research investigated genetic alteration effects from blood donation on blood cells with a specific focus on clonal hematopoiesis (CH) mutant cells responsible for disease risk.
Researchers investigated if repeated donation of blood could lead to the development of CH among donors. The researchers examined DNA from blood samples that originated from two elderly male groups: frequent donors exceeding 100 times and control donors who only donated blood fewer than ten times. Under the study, two groups of participants were included: frequent donors (FD with 217 members) and control donors (CD with 212 members) who were all above 60 years old. Biological researchers used peripheral blood leukocytes as subject matter for DNA sequencing since these white blood cells (WBCs) exist within the bloodstream of all donors. The research studied whether stem cell mutations that occur in blood stem cells change with repeated blood donation.
Researchers studied DNA extracted from blood collected from elderly male blood donors who donated more than 100 times and a group who had donated fewer than 10 times. A total of 429 participants were part of this research since they were all over 60 years old; the study divided these participants into two groups: 217 frequent donors (FD) and 212 control donors (CD). The DNA sequencing examined peripheral blood leukocytes found in the bloodstream to derive results from both groups of elderly males. The research design evaluated whether ongoing blood donations affect the genetic mutations within blood stem cells. The study was conducted between December 2019 and August 2023. Cohort 1 received blood donations between December 2019 and June 2020, with follow-ups from December 2020 to November 2021. Cohort 2 received blood donations in August 2023. Donors made their contributions at all German Red Cross Blood Service centers in Baden-Württemberg-Hessen.
The research received ethical approval from responsible committees before participants could sign their consent to join. The research discovered that regular blood donors maintained similar levels of clonal hematopoiesis frequency when compared to controls no matter which VAF (variant allele frequency) boundary point was employed during examination. Researchers found no differences in VAF results, which represent mutated allele proportions between participants who donated blood frequently and those in the control group.
The research study discovered that both groups demonstrated equivalent mutant variations without any major differences in the observed mutations. Mutations in DNMT3A and TET2 were frequently observed in both FD and CD groups, with DNMT3A being the most prevalent. The gene mutations carry minimal risk for blood-related cancer development. The study proved that regular blood donors did not possess an altered clonal hematopoiesis prevalence when compared against controls using all established VAF thresholds for evaluation. Blood tests revealed that the VAF quantity measuring mutated allele proportions was the same for donors as in the control group. The research showed that the examined mutations appeared at equivalent levels between both the frequent blood donors and control subjects. Mutations in genes DNMT3A and TET2 appeared equally frequently in both FD patients and CD patients, while DNMT3A mutations were discovered most.
The observed mutations typically present a minimal possibility of developing blood-related cancers. Research results documented that frequent blood donors exhibited DNMT3A mutations with larger numbers of frameshift along with stop codon mutations than observed among other mutation types. Lower stability scores identified these mutations as factors that would not sustain long-term blood cell development. The bone marrow expansion potential of mutations from the control group outperformed those found in the tested bloodstream donors because their mutations showed higher stability levels. The investigators found that mutations from DNMT3A had lower fitness scores in the FD patient group compared to those in the CD patient group, which indicates that their potential to survive and multiply in bone marrow was smaller. The research showed that DNMT3A mutations within FD patients exhibited characteristics such as increased incidence of frameshift and premature stop variants.
The bone marrow showed reduced expansion capability for these mutations rather than preleukemic cases because the fitness for long-term expansion was lower. The DNMT3A variants in FD subjects had a significantly lower s-value, with a mean fitness score of 10.5% per year, compared to 13.5% in CD subjects (p < 0.001). The study demonstrates that regular blood donation practices do not affect the distribution rates of clonal hematopoiesis within elderly patient groups. The regular blood donations did not influence the occurrence of CH genetic mutations in both persistent and sporadic donors.
According to this research, DNMT3A and TET2 mutations act as low-risk modifications that typically exclude the development of serious blood conditions. The absence of JAK2 mutations in frequent donors suggests a lower risk of developing high-risk genetic mutations associated with hematologic malignancies. The research delivers significant findings about how often people donate blood affects their blood stem cells and clonal hematopoiesis development.
References: Karpova D, Huerga Encabo H, Donato E, et al. Clonal Hematopoiesis Landscape in Frequent Blood Donors. Blood. 2025:blood.2024027999. doi:10.1182/blood.2024027999
