Blood, sweat, and tears: Red Blood Cell‐Omics study objectives, design, and recruitment activities

Abstract

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.

Frequent blood donations alter susceptibility of red blood cells to storage‐ and stress‐induced hemolysis

“…Of the 13,770 consented donors, 13,403 (97%) provided sufficient samples and data for inclusion in the present analysis (further information regarding the study design and population was published by Endres-Dighe et al 23 ). Participant sex and racial-ethnic distributions stratified by donation history are summarized in Table 1.…”

Genetic and behavioral modification of hemoglobin and iron status among first‐time and high‐intensity blood donors

“…The NHLBI REDS‐III RBC‐Omics Study was a multi‐center study enrolling 13,403 blood donors . This cohort was genotyped using a customized Affymetrix Axiom Array with approximately 879,000 single nucleotide polymorphisms (SNPs) .…”

“…Groups 5 (818 females) and 6 (1652 males) had at least 8 whole blood donations within the prior 2 years. Iron supplement and cigarette use were obtained by survey . Ferritin and CBC were performed as described …”

“…Finally, the G277S (rs1799899) mutation in Transferrin is associated with iron deficiency in menstruating women. 19 We evaluated blood donors participating in the Retrovirus Epidemiology Donor Study-II (REDS-II) Iron Status Evaluation (RISE) Study 3 and the REDS-III Red Blood Cell Omics (RBC-Omics) study 20 to assess relationships between donor genetics and behaviors on hemoglobin and iron status. Longitudinal analyses were performed in the RISE cohort to define the impact of iron supplements, cigarette smoking, H63D, C282Y, A736V, and G277S.…”

“…The NHLBI REDS-III RBC-Omics Study was a multi-center study enrolling 13,403 blood donors. 20 This cohort was genotyped using a customized Affymetrix Axiom Array with approximately 879,000 single nucleotide polymorphisms (SNPs). 22 Participants were stratified by sex and categorized into six groups that approximated the longitudinal groups ( Figure 1B), differing by selection of females with a previous low hemoglobin deferral, instead of frequent first-time females, who could not be defined because of the crosssectional study design.…”