Articles published on Blood Donation
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- New
- Research Article
- 10.7860/jcdr/2026/81510.22753
- Apr 1, 2026
- JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH
- Ajay Surendrasinh Taviyad + 3 more
Introduction: Blood donation is vital part of any blood transfusion services in healthcare. There are various Adverse Donor Reactions (ADRs) associated with blood donation. These reactions affect blood donation and, in terms supply of blood. Understanding the prevalence and nature of ADRs is crucial for improving the overall donor experience, so that the present study was done to estimate the incidence of ADRs among blood donors, along with typing such donors with reactions according to the National Blood Donor Vigilance Programme (Haemovigilance Program of India - HvPI). Aim: The present study was conducted to find out the incidences and types of ADRs among whole blood and apheresis donors. Materials and Methods: The present prospective observational cohort study was conducted at a blood centre attached to Tertiary Care Government hospital of South Gujarat, India, from February 2021 to December 2024, according to guidelines given by the Department of Biologicals, Government of India, under the National Haemovigilance Programme. During the present study analysis of ADRs among whole blood donors and apheresis donors, along with effect of gender, site of donation, and type of donation on ADRs. The analysis was done using two-tailed Chi-square test and odds ratios at 95% confidence interval. Results: Among total of 34,202 blood donations during the study period, the overall incidence of ADRs was 168 (0.49%). Majority of ADRs were Vasovagal Reactions (VVR), constituting 96.42% of all types. Most ADRs (56.54%, i.e., 95 out of 168 ADRs) occurred in donors aged 18-30 years, with first-time donors exhibiting a higher prevalence of 52.38%. Notably, ADRs were more frequent in females than in males (0.74% vs. 0.48%). Outdoor donation camps showed a higher rate of ADRs compared to in-house donations (0.51% vs. 0.38%), although these findings were not statistically significant (p-value >0.05 at 95% confidence interval). Conclusion: The present study highlighted the importance of age, gender, donation type, and donation site in relation to ADRs. Effective donor counselling and observation, especially for first-time donors, are crucial in minimising ADRs and enhancing donor safety. Understanding the factors influencing ADRs can be helpful to improve donor recruitment and retention, ultimately contributing to a safer and more sustainable blood donation system.
- New
- Research Article
- 10.1177/19375867251414968
- Apr 1, 2026
- HERD
- Minyoung Cerruti + 2 more
ObjectiveThis study investigates how privacy, distraction, and comfort in blood donation environments affect donors' stress and motivation, addressing critical challenges posed by ongoing blood shortages.BackgroundThe reluctance to donate blood is associated with donors' experience exacerbated by stress during the donation process and the quality of the donation environment. Despite known physical environmental influences on patient well-being in healthcare settings, its influence within blood donation settings remains underexplored.MethodsUsing an online survey with a virtual visualization technique, 400 college-aged participants rated their preferences and emotional responses to eight simulated blood drive bus environment settings.ResultsSettings combining privacy, positive distraction, and comfort significantly reduced stress and increased motivation compared to those with fewer interventions. Female and less experienced donors (nondonors, first-timers) particularly benefited from enhanced comfort and distraction, reporting lower fear and greater positive emotions. Cultural differences also influenced experiences.ConclusionsFindings highlight the potential of well-designed blood donation environments to reduce stress and enhance motivation, especially among younger, female, and less experienced donors, improving donation experiences and addressing critical blood shortage.
- New
- Research Article
- 10.1016/j.jcyt.2025.102037
- Apr 1, 2026
- Cytotherapy
- Tristan Rallon + 10 more
Post-thaw washing of cryopreserved hematopoietic stem cell products is essential to reduce dimethyl sulfoxide concentration and toxicity. This procedure is routinely performed in French cell therapy units. Following the discontinuation of the COBE2991 device, alternative technologies such as the LOVO Med automated closed system have been evaluated. We retrospectively compared the COBE2991 and LOVO Med for washing peripheral blood stem cells (PBSC) products and donor lymphocyte infusions (DLIs). A total of 946 products processed between September 2021 and October 2023 were included. The parameters assessed were recovery of CD34+, CD45+ and CD3+ cells, viability, processing time, infusion-related adverse events and engraftment. LOVO Med demonstrated a significantly higher median CD34+ cells recovery in autologous PBSCs group (88.5% vs. 84.9%; P = 0.0012). Post-thaw CD45+ viability remained acceptable in both groups, although it was slightly lower with LOVO Med (89.6% vs. 91.8%; P = 0.023). CD3+ yields and viabilities were similar between DLIs. Processing time was shorter with LOVO Med (59 vs. 69 min; P < 0.0001). No differences in adverse events or engraftment were observed. LOVO Med is a safe and efficient alternative to COBE2991 for post-thaw cell therapy product washing, with comparable clinical outcomes.
- New
- Research Article
- 10.1016/j.ijid.2026.108425
- Apr 1, 2026
- International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
- Michel M Yop Kite + 12 more
Epidemiology and safety challenges of major transfusion-transmitted pathogens in Cameroon: A systematic review and meta-analysis.
- New
- Research Article
- 10.1016/j.trim.2026.102364
- Apr 1, 2026
- Transplant immunology
- A Quintiliano + 6 more
The clinical relevance of non-HLA antibodies remains uncertain due to the lack of standardized assays. This study aimed to assess comparative reference values for non-HLA antibody profiles in a cohort of kidney transplant candidates on the deceased donor waiting list (WL group) with 0% calculated panel reactive antibodies (cPRA) and in healthy male blood donors (BD group). Serum samples from 81 transplant candidates in the WL group and 92 individuals in the BD group were analyzed using the LABScreen™ Autoantibody Assay, which detects antibodies against 33 non-HLA antigens. Antibody positivity was defined using manufacturer-defined 95th percentile cut-off thresholds (COTs). Group comparisons were performed using non-parametric statistical methods, correlation analyses, and hierarchical clustering. Non-HLA antibody binding varied widely across antigens and cohorts. The BD group showed significantly higher median fluorescence intensity (MFI) values than the WL group for most antigens, except CXCL9 and GAPDH. Binding differences were observed between the BD and WL cohorts for most antigens, except for ARHGDIB (p=0.565), NCL (p=0.552), and GDNF (p=0.08). Correlation analyses identified strong antigen pair associations (e.g., GDNF-REG3A, ρ=0.83). Antibody reactivity against PRKCZ and CHAF1B differed significantly between cohorts, with higher reactivity observed in the BD group than in the WL group. This study demonstrates substantial heterogeneity in non-HLA antibody reactivity across antigens, with consistently lower antibody detection in the WL group. These findings support the concept that immune modulation in transplant candidates may reduce detectable non-HLA antibody levels and provide a rationale for defining reference cut-off values, particularly at the 95th percentile, for this population.
- New
- Research Article
- 10.1016/j.envres.2026.123966
- Apr 1, 2026
- Environmental research
- Sarah-Maude Goulet + 5 more
Eastman Tritan™ copolyester, a novel plastic used as a replacement for bisphenols and manufactured utilizing three monomers, can be released from products, potentially entering biological fluids, and could exert estrogenic activity. Since neutrophils are inflammatory cells that express hormone receptors, we hypothesized that Tritan compounds could modulate neutrophil metabolism and function. Human neutrophils from the blood of healthy male and female donors were exposed in vitro to Tritan monomers, alone or combined with pro-inflammatory cytokines, and assessed for viability, metabolism, surface marker expression, and antimicrobial functions. Tritan compounds did not affect neutrophil viability but increased metabolic activity under inflammatory conditions. The production of CCL4/MIP-1β was reduced, while CXCL8/IL-8 was unchanged. Phagocytosis and reactive oxygen species production were altered in a dose-dependent manner, with the effect more pronounced in male neutrophils at lower doses and female neutrophils at higher doses. The expression of CD11b and CD16, adhesion and functional markers, was also modulated by Tritan monomers. These results indicate that Tritan and its monomers can alter neutrophil phenotype and function, potentially impairing host defence or contributing to dysregulated inflammation. These findings raise concerns about the safety of Tritan as an alternative plasticizer. Further research is needed to better understand the potential health risks of Tritan and its monomers, to help develop or update evidence-based regulations that protect public health.
- New
- Research Article
- 10.1016/j.virusres.2026.199702
- Apr 1, 2026
- Virus research
- Ebrahim Abbasi
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus transmitted by Aedes aegypti and Aedes albopictus. Despite favorable ecological conditions in southern Iran, data on CHIKV exposure in Bushehr Province are lacking. This study aimed to determine the seroprevalence of CHIKV-specific IgG antibodies and assess potential viral circulation. A cross-sectional seroepidemiological survey was conducted from July to September 2023 in ten cities across Bushehr Province. Serum samples (n = 180) collected from volunteers at hospitals and blood donation centers were tested for CHIKV-specific IgG antibodies using a commercial ELISA kit. Of the 180 serum samples analyzed, five tested positive for CHIKV IgG antibodies, yielding an overall seroprevalence rate of 2.78%. Seropositive individuals were identified in Bushehr, Dashtestan, and Dashti cities, indicating localized and possibly silent transmission. This study provides the first serological evidence of CHIKV exposure in Bushehr Province. The findings underscore the potential for local transmission in areas where competent Aedes vectors are present and highlight the urgent need for sustained vector surveillance, early warning systems, and public health preparedness in southern Iran.
- New
- Research Article
1
- 10.1016/j.transci.2026.104392
- Apr 1, 2026
- Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis
- Tanya Nadia Glatt + 15 more
Status of donor and clinical apheresis across the African continent: A report of a 2025 survey.
- New
- Research Article
1
- 10.1016/j.transci.2026.104397
- Apr 1, 2026
- Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis
- Dilys John-Teye
A donor and patient apheresis program in Ghana.
- Research Article
- 10.1111/trf.70167
- Mar 12, 2026
- Transfusion
- Huijun Zhu + 7 more
Surface antigens on platelets and neutrophils-including human platelet antigens (HPA), human neutrophil antigens (HNA), and CD36-are critical determinants of compatibility in platelet transfusion. To address the need for high-throughput genotyping, this study developed a method for simultaneous detection of 35 HPA systems, 5 HNA systems, and CD36 polymorphisms based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) technology. Specific primers for amplification and single-base extension were designed, distributing 53 loci into two multiplex pools. Genotyping was performed using the MassARRAY MS platform. Method accuracy was verified by Sanger sequencing for all 53 loci (34 samples) and flow cytometric serotyping for HPA-1, -3, -5 and CD36. The validated method was then applied to genotype 8100 random blood donors to establish a platelet donor database. An MS-based genotyping method was successfully established, covering 53 loci distributed across two multiplex pools. All verified samples yielded results consistent with those obtained through Sanger sequencing, serotyping, or flow cytometry. Using this method, a platelet donor genotyping database comprising 8100 donors was created, identifying rare HPA alleles (1 case each of HPA-8b/-9b/-11b/-16b/-25b; 2 of HPA-17b/-30b; 3 of HPA-20b). We successfully developed an MS panel capable of detecting all currently known HPAs, HNAs, and the CD36 antigen, overcoming limitations of previous methods related to non-specific HNA-1 amplification. This method also demonstrated its efficacy in establishing a large-scale platelet donor database, and rare allele data support precise transfusion matching for special patients.
- Research Article
- 10.1159/000551415
- Mar 12, 2026
- Journal of innate immunity
- Louise V Duebel + 7 more
Neutrophils are the most abundant innate immune cells in the peripheral blood and eliminate bacteria through phagocytosis and antimicrobial mechanisms. Early during infection, they often encounter high bacterial loads before full recruitment. Individual neutrophils can ingest many bacteria, but it remains unclear how high bacterial loads per neutrophil affect intracellular killing. Neutrophils were isolated from healthy donor blood by fluorescence-activated cell sorting (FACS). Intracellular bacterial load was quantified using imaging flow cytometry to measure spot counts and green fluorescent protein (GFP) intensity after exposure to GFP-expressing Staphylococcus aureus. A single-cell killing assay assessed intracellular killing across bacterial-load categories by sorting individual GFP+ neutrophils into 384-well plates and counting wells with outgrowth after 100 hours. Phagolysosomal acidification was measured using dual-labeled (pH-sensitive pHrodo and pH-insensitive PromoFluor 520 LSS NHS ester [PF520]) S. aureus bioparticles. Bacterial uptake by neutrophils was highly heterogeneous in vivo and in vitro. GFP spot counts strongly correlated with GFP intensity (R² = 0.66), allowing stratification into GFP fluorescence intensity categories. In the single-cell killing assay, higher bacterial loads per neutrophil were associated with reduced intracellular killing (χ²(4) = 11.72, p = 0.0003). Higher bacterial loads per neutrophil corresponded with diminished phagolysosomal acidification capacity (χ²(4) = 24.00, p < 0.0001). Neutrophils ingesting higher bacterial loads exhibit reduced intracellular killing, likely due to decreased phagolysosomal acidification. These findings highlight how bacterial load per neutrophil shapes antimicrobial capacity and early infection control.
- Research Article
- 10.1111/vox.70231
- Mar 11, 2026
- Vox sanguinis
- Jian Ou-Yang + 5 more
The coronavirus disease 2019 pandemic in 2020 caused severe disruptions to blood supplies in China. In response, a collaborative strategy known as the 'Baby Dad Blood Donation Project' (BDBDP) was implemented by the Guangzhou Blood Center and associated hospitals. The current research aims to evaluate the effects of this project. A match-pair study design was adopted, involving three male participant groups: BDBDP participants (Father donors [F-donors]); spontaneous donors at mobile blood drives or apheresis donation stations (Spontaneous donors [S-donors]); and Non-donors (N-donors) who had never donated blood. F- and S-donors were matched by age, donation frequency and volume. N-donors, sourced from an online marketplace, were age-matched with F-donors. Following a 1:1:1 pairing, 535 males were selected per group. Participants completed a questionnaire and were followed for 2 years. In total, 104 (19.4%) F-donors and 198 (37.0%) S-donors re-donated blood within 2 years (p < 0.001). Among first-time donors, 36 (10.6%) F-donors re-donated compared to 91 (26.7%) donors. N-donors exhibited a significantly lower first-time donation rate (26 (4.8%), ps < 0.001). Saving lives (p = 0.875) was the primary motive of present blood donation among all donors, but F-donors were more likely to donate blood because of preferential blood use (p < 0.001). Lack of motivation emerged as the primary reason why first-time F-donors had not donated previously. The BDBDP effectively encouraged first-time donations among the fathers-to-be and raised awareness about blood donation. However, re-donation rates were modest, indicating the need for ongoing engagement strategies to sustain donor participation.
- Research Article
- 10.1371/journal.pntd.0014056.r004
- Mar 10, 2026
- PLOS Neglected Tropical Diseases
- Weerawat Phuklia + 14 more
BackgroundScrub typhus and murine typhus, caused by Orientia tsutsugamushi and Rickettsia typhi, respectively, are important causes of febrile illness in Laos. Although several studies have assessed rickettsial infection in selected provinces, the nationwide distribution remains unclear. This study aimed to estimate exposure to scrub typhus group (STG) and typhus group (TG) across twelve provinces of Laos and identify potential hotspots.MethodologyWe screened 1,200 serum samples from blood donors (100 per province) for STG and TG IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Samples with optical density ≥ 0.5 were confirmed by immunofluorescence assays (IFA).ResultsOverall seroprevalence was 7.26% (95%CI:5.93-8.87) for STG and 4.09% (95% CI:3.11-5.37) for TG. STG seroprevalence was highest in Huaphan (27%), Oudomxay (19%) and Xiangkhuang (17%), all in northern Laos. TG seroprevalence was 10% in both Oudomxay (north) and Attapue (south). Compared with Vientiane Capital, these provinces had significantly higher seropositivity. No significant association was observed with age group. STG seropositivity was higher in males, whereas TG seropositivity was higher in females.ConclusionRickettsial infections are widespread in Laos, with STG seroprevalence concentrated in the north and TG seroprevalence present in both the north and south, guiding future research priorities and informing targeted public health interventions.
- Research Article
- 10.1111/trf.70137
- Mar 9, 2026
- Transfusion
- Pedro Suárez-Artime + 5 more
Effective recruitment and retention of donors are essential for the supply of blood components and blood-derived medicines. In many high-income Western countries, there is an imbalance between demand and production of blood-derived medicines. Motivational factors behind donations range from altruism and health concerns to incentives or responding to a need from friends or family. Motivations might differ according to beliefs and social norms. The aim of this review was to identify the motivations that influence blood and plasma donation behavior in high-income Western countries. We conducted a scoping review following the PRISMA-ScR guidelines. A comprehensive search was performed in MEDLINE, EMBASE and CINAHL for studies published from 2013 onwards that examined motivations for blood or plasma donation in high-income Western countries. Reported motivations were coded and grouped into predefined categories and subcategories. Thirty-eight studies including 147,010 participants met the inclusion criteria. Most studies assessed motivations for blood donation, while few focused on plasma donation. Across studies, prosocial motivations were the most frequently reported drivers of donation. Among blood donors, altruistic reasons such as helping others and social responsibility predominated. Non-donors more often cited collectivist motives, such as donating when a friend or relative needed blood. For plasma donation, prosocial motivations remained important, although incentives were cited more often than for blood donation. Prosocial motivations, particularly altruism and personal values, are the main drivers of blood and plasma donation in high-income Western countries. However, motivations vary across donor groups and between blood and plasma donation.
- Research Article
- 10.1111/vox.70229
- Mar 9, 2026
- Vox sanguinis
- Timo Asikainen + 10 more
To meet the long-term demand for blood products while preserving donor health in the long run, blood establishments must recruit a sufficient number of new donors annually. To determine what will suffice, it is essential to be able to forecast future blood donation volumes as a function of new donors using estimates based on historical donation activity. Donor (n = 11,629,873) and donation data (n = 64,510,294) extracted from operational information systems of seven blood establishments were transformed into anonymous donation activity data (grouped by blood establishment, sex and blood group) in the form of time series of mean number of donations per donor, indexed by years since first donation. Linear models were fitted to the time series using ordinary least squares. Out of the various estimated models, the best fit (mean R2 over blood establishments 99.95%) for past mean donation activity was achieved when regressing the logarithm of cumulative donation activity on the logarithm of years since first donation and an indicator variable for the year of first donation. In addition to the predictions, comparison of the estimated parameters revealed that there are significant differences between blood establishments, translating to differences in the expected number of donations accumulated over the lifetime of a donor. Average donation activity can be modelled using a few variables and simple models, with high precision. The estimates can be used to create forecasts of future donation volumes, which in turn can be useful in long-term blood donation management.
- Research Article
- 10.1111/vox.70232
- Mar 9, 2026
- Vox sanguinis
- Jaid Debrah + 10 more
The For the Assessment of Individualized Risk (FAIR) framework, introduced by NHS Blood and Transplant (NHSBT) in 2021, aims to reduce stigma and improve equity in blood donor selection, particularly for gay, bisexual and other men who have sex with men (GBMSM). While pre-exposure prophylaxis (PrEP) is highly effective at preventing sexual transmission of human immunodeficiency virus, its declared use excludes individuals from blood donation. This study examined PrEP use among male blood donors with current or past syphilis in England to evaluate guideline compliance and implications for blood safety. Residual plasma samples from syphilis-positive male blood donors collected in 2023 were tested for PrEP. These data were combined with two previous studies of syphilis-positive donors conducted between July 2018 and June 2024, incorporating demographics and reported PrEP use. The rate of syphilis-positive blood donations increased from 4.09 to 10.32 per 100,000 donations between 2018 and 2024 (p = 0.048, Mann-Kendall trend test) with a rising proportion of past syphilis cases attributed to GBMSM (18%-37%; p = 0.004, Fisher's test, p = 0.001 Mann-Kendall test); 7.1% of syphilis-positive blood samples from male blood donors tested positive for PrEP in 2023, indicating frequent non-compliance with donation guidelines. Persistent PrEP use among syphilis-positive donors since 2018 suggests gaps in donor education regarding eligibility. Targeted public health interventions, particularly for younger GBMSM, are needed to strengthen sexual health education, PrEP messaging and awareness of donation criteria. Further research into other infections associated with high-risk sexual behaviour is warranted.
- Research Article
- 10.1186/s12879-026-13030-1
- Mar 9, 2026
- BMC infectious diseases
- Komal Iqbal + 7 more
Prevalence and pattern of transfusion transmitted infections among blood donors visiting a tertiary care hospital, Pakistan.
- Research Article
- 10.1111/jvh.70156
- Mar 9, 2026
- Journal of viral hepatitis
- Montserrat Fraga + 11 more
Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide. Whereas HEV infection is typically self-limiting, rare cases of prolonged cholestasis have been reported. The underlying mechanisms remain unclear, though host genetic variation may contribute. This study aimed to investigate the role of genetic predisposition in HEV-induced prolonged cholestasis by analysing variants in genes associated with hepatocanalicular transport. We performed a retrospective review of medical records from three university centres in Switzerland and Germany and identified five immunocompetent patients with prolonged cholestasis following acute HEV infections. Genetic analysis using next-generation sequencing included a panel of five genes involved in cholestatic liver diseases (ATP8B1, ABCB11, ABCB4, ABCC2 and MYO5B). Variant frequencies were evaluated using population reference databases and compared with a genetically characterised cohort of asymptomatic HEV-infected blood donors. All five patients were male, with a median age of 59 years. The median duration of cholestasis exceeded 77 days. Two patients exhibited potentially pathogenic heterozygous variants: ATP8B1 p.N45T in one patient and MYO5B p.K429R in another. Additionally, common ABCB11 variants were detected in all patients, which might have contributed to cholestatic clinical presentation. In the asymptomatic HEV-infected controls, the MYO5B p.K429R variant was absent, whereas the ATP8B1 p.N45T variant was detected in only one individual in a heterozygous state. These case series illustrate that host genetics might influence the severity of HEV infection, particularly prolonged cholestatic jaundice. Further research is needed to explore the interaction between viral infections and host genetics in liver disorders.
- Research Article
- 10.1111/trf.70148
- Mar 7, 2026
- Transfusion
- Sara O Dionne + 3 more
Abstract Background Accurate ABO determination is critical for safe deceased donor organ allocation. Weak or variant ABO subgroups may not be reliably detected by routine serologic testing, especially under urgent conditions or following transfusion. Such limitations can result in discrepant ABO assignments with potential implications for transplant safety. Study Design and Methods We describe a deceased organ donor with discordant ABO typing results reported by two laboratories. Serologic testing was performed using gel agglutination methods on independently collected specimens. Due to persistent discrepancies, ABO genotyping was performed using real‐time polymerase chain reaction to resolve the donor's blood group. Results Initial serologic testing identified the donor as AB RhD+ at one laboratory, while a second laboratory reported B RhD+ results. Repeat serologic evaluation demonstrated weak and variable A antigen reactivity, suggestive of a weak A subgroup. Molecular genotyping performed on specimens from both laboratories identified an AwB genotype, confirming the presence of a weak A allele. Because molecular results were not available prior to organ allocation and the discrepancy could not be resolved in real time, the donor was conservatively classified as AB for allocation purposes. Discussion This case highlights the vulnerability of routine serologic testing to misclassification of rare weak ABO subgroups. Integration of molecular genotyping with serologic testing can provide resolution of ABO discrepancies and enhance transplant safety. This case demonstrates a policy‐relevant gap in current ABO determination workflows for deceased donors. Lack of standardized inter‐laboratory data sharing and limited access to rapid molecular testing may unnecessarily restrict organ utilization.
- Research Article
- 10.3390/ijms27052410
- Mar 5, 2026
- International journal of molecular sciences
- Rebekka Hillingsø + 12 more
Individuals with C282Y/C282Y in the hemochromatosis HFE gene have increased iron levels, which catalyze the formation of reactive oxygen species, and an increased risk of diabetes. These individuals may have disproportionately lower hemoglobin A1c (HbA1c) due to increased erythrocyte turnover, decreased erythrocyte counts, and/or an increased mean corpuscular hemoglobin concentration (MCHC). In the Copenhagen General Population Study (N = 103,734) and the Danish General Suburban Population Study (GESUS, N = 20,003), we investigated the association between C282Y/C282Y (N = 399) and other HFE genotypes with erythrocyte count, MCHC, mean corpuscular volume (MCV), red cell distribution width (RDW), and high-sensitivity C-reactive protein (hsCRP). In GESUS, we additionally investigated the association with oxidative stress (by 8-oxo-7,8-dihydroguanosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine), reticulocyte count, reticulocyte hemoglobin, reticulocyte percentage as a proxy for erythrocyte turnover, and HbA1c in linear regressions adjusted for age, sex, cohort, and blood donation. We investigated the mediation between HFE genotype and HbA1c. Compared to non-carriers, individuals with C282Y/C282Y had increased p-iron, transferrin saturation, ferritin, hsCRP, oxidative stress, reticulocyte counts, reticulocyte percentage (1.24% vs. 1.06%, p = 1.7 × 10-5) as a proxy for erythrocyte turnover, MCHC (344 vs. 340 g/L, p = 1.7 × 10-12), MCH, MCV, reticulocyte hemoglobin, p-glucose (5.6 vs. 5.4, p = 0.007), bilirubin, and LDH and decreased RDW, erythrocyte counts (4.49 × 1012/L vs. 4.61 × 1012/L, p = 6.1 × 10-11), estimated erythrocyte survival, and HbA1c (36 vs. 38 mmol/mol, p = 0.01). The associations were similar, although attenuated, for other HFE genotypes. The association between the HFE genotype and decreased HbA1c was partially mediated by increased transferrin saturation, MCHC, MCV, and decreased erythrocyte count, but not by hsCRP, reticulocyte count, oxidative stress, or blood donation. In conclusion, while C282Y/C282Y and other HFE genotypes increased erythrocyte turnover, the disproportionately decreased HbA1c level was explained by fewer but larger erythrocytes filled with more hemoglobin and removed earlier from circulation, thus diluting the relative concentration of intracellular glucose per hemoglobin molecule.