BACKGROUND
Genetic determinants may underlie the susceptibility of red blood cells (RBCs) to hemolyze in vivo and during routine storage. This study characterized the reproducibility and dynamics of ...in vitro hemolysis variables from a subset of the 13,403 blood donors enrolled in the RBC‐Omics study.
STUDY DESIGN AND METHODS
RBC‐Omics donors with either low or high hemolysis results on 4°C‐stored leukoreduced (LR)‐RBC samples from enrollment donations stored for 39 to 42 days were recalled 2 to 12 months later to donate LR‐RBCs. Samples of stored LR‐RBCs from the unit and from transfer bags were evaluated for spontaneous and stress‐induced hemolysis at selected storage time points. Intradonor reproducibility of hemolysis variables was evaluated in transfer bags over two donations. Hemolysis data at serial storage time points were generated on LR‐RBCs from parent bags and analyzed by site, sex, race/ethnicity, and donation frequency.
RESULTS
A total of 664 donors were successfully recalled. Analysis of intradonor reproducibility revealed that osmotic and oxidative hemolysis demonstrated good and moderate reproducibility (Pearson's r = 0.85 and r = 0.53, respectively), while spontaneous hemolysis reproducibility was poor (r = 0.40). Longitudinal hemolysis in parent bags showed large increases over time in spontaneous (508.6%) and oxidative hemolysis (399.8%) and smaller increases in osmotic (9.4%) and mechanical fragility (3.4%; all p < 0.0001).
CONCLUSION
Spontaneous hemolysis is poorly reproducible in donors over time and may depend on site processing methods, while oxidative and osmotic hemolysis were reproducible in donors and hence could reflect consistent heritable phenotypes attributable to genetic traits. Spontaneous and oxidative hemolysis increased over time of storage, whereas osmotic and mechanical hemolysis remained relatively stable.
BACKGROUND
Frequent whole blood donations increase the prevalence of iron depletion in blood donors, which may subsequently interfere with normal erythropoiesis. The purpose of this study was to ...evaluate the associations between donation frequency and red blood cell (RBC) storage stability in a racially/ethnically diverse population of blood donors.
STUDY DESIGN
Leukoreduced RBC concentrate–derived samples from 13,403 donors were stored for 39 to 42 days (1–6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Iron status was evaluated by plasma ferritin measurement and self‐reported intake of iron supplements. Donation history in the prior 2 years was obtained for each subject.
RESULTS
Frequent blood donors enrolled in this study were likely to be white, male, and of older age (56.1 ± 5.0 years). Prior donation intensity was negatively associated with oxidative hemolysis (p < 0.0001) in multivariate analyses correcting for age, sex, and race/ethnicity. Increased plasma ferritin concentration was associated with increased RBC susceptibility to each of the three measures of hemolysis (p < 0.0001 for all), whereas self‐reported iron intake was associated with reduced susceptibility to osmotic and oxidative hemolysis (p < 0.0001 for both).
CONCLUSIONS
Frequent blood donations may alter the quality of blood components by modulating RBC predisposition to hemolysis. RBCs collected from frequent donors with low ferritin have altered susceptibility to hemolysis. Thus, frequent donation and associated iron loss may alter the quality of stored RBC components collected from iron‐deficient donors. Further investigation is necessary to assess posttransfusion safety and efficacy in patients receiving these RBC products.
BACKGROUND
The Red Blood Cell (RBC)‐Omics study was initiated to build a large data set containing behavioral, genetic, and biochemical characteristics of blood donors with linkage to outcomes of the ...patients transfused with their donated RBCs.
STUDY DESIGN AND METHODS
The cohort was recruited from four US blood centers. Demographic and donation data were obtained from center records. A questionnaire to assess pica, restless leg syndrome, iron supplementation, hormone use, and menstrual and pregnancy history was completed at enrollment. Blood was obtained for a complete blood count, DNA, and ferritin testing. A leukocyte‐reduced RBC sample was transferred to a custom storage bag for hemolysis testing at Storage Days 39 to 42. A subset was recalled to evaluate the kinetics and stability of hemolysis measures.
RESULTS
A total of 13,403 racially/ethnically diverse (12% African American, 12% Asian, 8% Hispanic, 64% white, and 5% multiracial/other) donors of both sexes were enrolled and ranged from 18 to 90 years of age; 15% were high‐intensity donors (nine or more donations in the prior 24 mo without low hemoglobin deferral). Data elements are available for 97% to 99% of the cohort.
CONCLUSIONS
The cohort provides demographic, behavioral, biochemical, and genetic data for a broad range of blood donor studies related to iron metabolism, adverse consequences of iron deficiency, and differential hemolysis (including oxidative and osmotic stress perturbations) during RBC storage. Linkage to recipient outcomes may permit analysis of how donor characteristics affect transfusion efficacy. Repository DNA, plasma, and RBC samples should expand the usefulness of the current data set.
See article on page 2–5, in this issue
BACKGROUND
The optimal approach for reducing iron depletion (ID) in blood donors may vary depending on biologic or behavioral differences across donors.
STUDY DESIGN AND METHODS
More than 12,600 ...successful whole blood donors were enrolled from four US blood centers for ferritin testing. The study population was enriched for racial/ethnic minorities (1605 African American, 1616 Asian, 1023 Hispanic). Subjects completed questionnaires on ID risk factors. Logistic regression identified predictors of absent iron stores (AIS; ferritin <12 ng/mL) and low ferritin (LF; ferritin <26 ng/mL).
RESULTS
Across all subjects, 19% had AIS and 42% had LF, with a sharp increase in risk observed with increasing donation intensity and among women a large decrease in risk in those more than 50 years old. When other factors were controlled for, African American and Asian donors showed 20% to 25% decreased risk for AIS compared to non‐Hispanic Caucasian donors, while Hispanic donors had 25% higher risk. Daily iron supplementation reduced risk for LF and AIS by 30% to 40%, respectively, while the benefit from less frequent use was lower (7%‐19% protection). Regular antacid use was associated with at least 20% increment to risk. Use of oral contraceptives or estrogen in females reduced risk by 16% to 22%, while males who reported supplemental testosterone use had a 50% to 125% greater risk for LF and AIS.
CONCLUSIONS
This study confirms high prevalence of LF and AIS in US donors and the principal risk factors of age, sex, and donation frequency. Additional demographic and behavioral risk factors of secondary importance might allow for refinement of ID mitigation strategies.
Background. The evolutionary pressure of endemic malaria and other erythrocytic pathogens has shaped variation in genes encoding erythrocyte structural and functional proteins, influencing responses ...to hemolytic stress during transfusion and disease. Methods. We sought to identify such genetic variants in blood donors by conducting a genome-wide association study (GWAS) of 12,353 volunteer donors, including 1,406 African Americans, 1,306 Asians, and 945 Hispanics, whose stored erythrocytes were characterized by quantitative assays of in vitro osmotic, oxidative, and cold-storage hemolysis. Results. GWAS revealed 27 significant loci (P < 5 * 10.sup.-8), many in candidate genes known to modulate erythrocyte structure, metabolism, and ion channels, including SPTA1, ALDH2, ANK1, HK1, MAPKAPK5, AQP1, PIEZO1, and SLC4A1/band 3. GWAS of oxidative hemolysis identified variants in genes encoding antioxidant enzymes, including GLRX, GPX4, G6PD, and SEC14L4 (Golgi-transport protein). Genome-wide significant loci were also tested for association with the severity of steady-state (baseline) in vivo hemolytic anemia in patients with sickle cell disease, with confirmation of identified SNPs in HBA2, G6PD, PIEZO1, AQP1, and SEC14L4. Conclusions. Many of the identified variants, such as those in G6PD, have previously been shown to impair erythrocyte recovery after transfusion, associate with anemia, or cause rare Mendelian human hemolytic diseases. Candidate SNPs in these genes, especially in polygenic combinations, may affect RBC recovery after transfusion and modulate disease severity in hemolytic diseases, such as sickle cell disease and malaria.
Observational studies are needed to demonstrate real-world vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes. Our objective was to conduct a ...review of published SARS-CoV-2 VE articles, supplemented by preprints, during the first 6 months of COVID-19 vaccine availability. This review compares the effectiveness of completing the primary COVID-19 vaccination series against multiple SARS-CoV-2 disease presentations and disease severity outcomes in three population groups (general population, frontline workers, and older adults). Four hundred and seventy-one published articles and 47 preprints were identified. After title and abstract screening and full article review, 50 studies (28 published articles, 22 preprints) were included. VE results were reported for five COVID-19 vaccines and four combinations of COVID-19 vaccines. VE results for BNT162b2 were reported in 70.6% of all studies. Seventeen studies reported variant specific VE estimates; Alpha was the most common. This comprehensive review demonstrates that COVID-19 vaccination is an important tool for preventing COVID-19 morbidity and mortality among fully vaccinated persons aged 16 years and older and serves as an important baseline from which to follow future trends in COVID-19 evolution and effectiveness of new and updated vaccines.
Infectious disease threats, like the 2002 severe acute respiratory syndrome coronavirus (SARS-CoV) disease, 2009 pandemic influenza A (H1N1), and the current coronavirus disease 2019 (COVID-19), pose ...multisectoral risk with the potential for wide-ranging socioeconomic disruption. In our globally intertwined economy, the impact of such events can elicit economic shock waves that reach far beyond the country of origin. Review of the 2018 Fortune 500 company 10-K filings shows the majority did not document perceived risks associated with epidemics, outbreaks, or pandemics. Enhanced engagement and investment of the public and private sectors in advancing global health security is needed to effectively prevent, detect, and respond to infectious disease events and ensure U.S. economic security.
Agent-based models (ABMs) describe and simulate complex systems comprising unique agents, or individuals, while accounting for geospatial and temporal variability among dynamic processes. ABMs are ...increasingly used to study healthcare-associated infections (ie, infections acquired during admission to a healthcare facility), including
infection, currently the most common healthcare-associated infection in the United States. The overall burden and transmission dynamics of healthcare-associated infections, including
infection, may be influenced by community sources and movement of people among healthcare facilities and communities. These complex dynamics warrant geospatially explicit ABMs that extend beyond single healthcare facilities to include entire systems (eg, hospitals, nursing homes and extended care facilities, the community). The agents in ABMs can be built on a synthetic population, a model-generated representation of the actual population with associated spatial (eg, home residence), temporal (eg, change in location over time), and nonspatial (eg, sociodemographic features) attributes. We describe our methods to create a geospatially explicit ABM of a major regional healthcare network using a synthetic population as microdata input. We illustrate agent movement in the healthcare network and the community, informed by patient-level medical records, aggregate hospital discharge data, healthcare facility licensing data, and published literature. We apply the ABM output to visualize agent movement in the healthcare network and the community served by the network. We provide an application example of the ABM to
infection using a natural history submodel. We discuss the ABM's potential to detect network areas where disease risk is high; simulate and evaluate interventions to protect public health; adapt to other geographic locations and healthcare-associated infections, including emerging pathogens; and meaningfully translate results to public health practitioners, healthcare providers, and policymakers.
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