Frequent blood donations alter susceptibility of red blood cells to storage- and stress-induced hemolysis
Corresponding Author
Tamir Kanias
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Address reprint requests to: Tamir Kanias, Vitalant Research Institute, 717 Yosemite Street, Denver, CO 80230; e-mail: [email protected]Search for more papers by this authorMars Stone
Blood Systems Research Institute, San Francisco, and Department of Laboratory Medicine, University of California, San Francisco, California
Search for more papers by this authorYuelong Guo
RTI International, Research Triangle Park, North Carolina
Search for more papers by this authorMarion C. Lanteri
Blood Systems Research Institute, San Francisco, and Department of Laboratory Medicine, University of California, San Francisco, California
Search for more papers by this authorBryan R. Spencer
American Red Cross Blood Services, Dedham, Massachusetts
Search for more papers by this authorDarrell J. Triulzi
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
The Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
Search for more papers by this authorJoseph E. Kiss
The Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
Search for more papers by this authorEdward L. Murphy
Blood Systems Research Institute, San Francisco, and Department of Laboratory Medicine, University of California, San Francisco, California
Search for more papers by this authorSteve Kleinman
University of British Columbia, Victoria, British Columbia, Canada
Search for more papers by this authorMark T. Gladwin
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorMichael P. Busch
Blood Systems Research Institute, San Francisco, and Department of Laboratory Medicine, University of California, San Francisco, California
MPB and AEM contributed equally to the manuscript.Search for more papers by this authorAlan E. Mast
Blood Research Institute, Blood Center of Wisconsin, and Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee
MPB and AEM contributed equally to the manuscript.Search for more papers by this authorfor the NHLBI Recipient Epidemiology Donor Evaluation Study (REDS)-III Program
Search for more papers by this authorCorresponding Author
Tamir Kanias
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Address reprint requests to: Tamir Kanias, Vitalant Research Institute, 717 Yosemite Street, Denver, CO 80230; e-mail: [email protected]Search for more papers by this authorMars Stone
Blood Systems Research Institute, San Francisco, and Department of Laboratory Medicine, University of California, San Francisco, California
Search for more papers by this authorYuelong Guo
RTI International, Research Triangle Park, North Carolina
Search for more papers by this authorMarion C. Lanteri
Blood Systems Research Institute, San Francisco, and Department of Laboratory Medicine, University of California, San Francisco, California
Search for more papers by this authorBryan R. Spencer
American Red Cross Blood Services, Dedham, Massachusetts
Search for more papers by this authorDarrell J. Triulzi
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
The Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
Search for more papers by this authorJoseph E. Kiss
The Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
Search for more papers by this authorEdward L. Murphy
Blood Systems Research Institute, San Francisco, and Department of Laboratory Medicine, University of California, San Francisco, California
Search for more papers by this authorSteve Kleinman
University of British Columbia, Victoria, British Columbia, Canada
Search for more papers by this authorMark T. Gladwin
Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorMichael P. Busch
Blood Systems Research Institute, San Francisco, and Department of Laboratory Medicine, University of California, San Francisco, California
MPB and AEM contributed equally to the manuscript.Search for more papers by this authorAlan E. Mast
Blood Research Institute, Blood Center of Wisconsin, and Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee
MPB and AEM contributed equally to the manuscript.Search for more papers by this authorfor the NHLBI Recipient Epidemiology Donor Evaluation Study (REDS)-III Program
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST
DT serves as a paid consultant to Fresenius Kabi. AM receives research grant funding from Novo Nordisk. The remaining authors have disclosed no conflicts of interest.
Supporting Information
Filename | Description |
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trf14998-sup-0001-supinfo.docxWord 2007 document , 4.5 MB |
Fig. S1. Race-ethnicity distributions of storage or stress-induced hemolysis at selected categories of donation frequency in prior 24 months. RBC concentrates from male or female donors ages 18–90 years old were stored (1–6°C) for 39 to 42 days in transfer bags and tested for storage or stress-induced hemolysis as described in Materials and Methods. (A) Percent AAPH-induced oxidative hemolysis (150 mmol/L, 1.5 h, 37°C) (n = 10,476). (B) Percent osmotic hemolysis (n = 12,799). (C) Percent spontaneous storage hemolysis (n = 12,753). Table S1. Percent storage, oxidative or osmotic hemolysis in each donation history category (0, 1–4, 5–8, and 9+) |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Jordan A, Chen D, Yi QL, et al. Assessing the influence of component processing and donor characteristics on quality of red cell concentrates using quality control data. Vox Sang 2016; 111: 8-15.
- 2Tzounakas VL, Georgatzakou HT, Kriebardis AG, et al. Donor variation effect on red blood cell storage lesion: a multivariable, yet consistent, story. Transfusion 2016; 56: 1274-86.
- 3Kanias T, Gladwin MT. Nitric oxide, hemolysis, and the red blood cell storage lesion: interactions between transfusion, donor, and recipient. Transfusion 2012; 52: 1388-92.
- 4Kanias T, Lanteri MC, Page GP, et al. Ethnicity, sex, and age are determinants of red blood cell storage and stress hemolysis: results of the REDS-III RBC-Omics study. Blood Adv 2017; 1: 1132-41.
- 5Kiss JE, Birch RJ, Steele WR, et al. Quantification of body iron and iron absorption in the REDS-II donor iron status evaluation (RISE) study. Transfusion 2017; 57: 1656-64.
- 6Cable RG, Glynn SA, Kiss JE, et al. Iron deficiency in blood donors: the REDS-II donor iron status evaluation (RISE) study. Transfusion 2012; 52: 702-11.
- 7Bialkowski W, Kiss JE, Wright DJ, et al. Estimates of total body iron indicate 19 mg and 38 mg oral iron are equivalent for the mitigation of iron deficiency in individuals experiencing repeated phlebotomy. Am J Hematol 2017; 92: 851-7.
- 8Cable RG, Brambilla D, Glynn SA, et al. National heart L, blood institute recipient E, donor evaluation S, III. Effect of iron supplementation on iron stores and total body iron after whole blood donation. Transfusion 2016; 56: 2005-12.
- 9Bialkowski W, Bryant BJ, Schlumpf KS, et al. The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention. Vox Sang 2015; 108: 178-85.
- 10Cable RG, Birch RJ, Spencer BR, et al. The operational implications of donor behaviors following enrollment in STRIDE (strategies to reduce iron deficiency in blood donors). Transfusion 2017; 57: 2440-8.
- 11Bryant BJ, Yau YY, Arceo SM, et al. Iron replacement therapy in the routine management of blood donors. Transfusion 2012; 52: 1566-75.
- 12Radtke H, Tegtmeier J, Rocker L, et al. Daily doses of 20 mg of elemental iron compensate for iron loss in regular blood donors: a randomized, double-blind, placebo-controlled study. Transfusion 2004; 44: 1427-32.
- 13Kiss JE. Laboratory and genetic assessment of iron deficiency in blood donors. Clin Lab Med 2015; 35: 73-91.
- 14Lefrere JJ, Hermine O. The real superdonors. Transfusion 2014; 54: 2431-3.
- 15Mast AE, Foster TM, Pinder HL, et al. Behavioral, biochemical, and genetic analysis of iron metabolism in high-intensity blood donors. Transfusion 2008; 48: 2197-204.
- 16Bandyopadhyay S, Brittenham GM, Francis RO, et al. Iron-deficient erythropoiesis in blood donors and red blood cell recovery after transfusion: initial studies with a mouse model. Blood Transfus 2017; 15: 158-64.
- 17Lanteri MC, Kanias T, Keating S, et al. Intra-donor reproducibility and changes in hemolytic parameters during red blood cell storage: results of recall phase of the REDS-III RBC-Omics study. Transfusion 2019; 59: 79-88.
- 18Zwart A, van Assendelft OW, Bull BS, et al. Recommendations for reference method for haemoglobinometry in human blood (ICSH standard 1995) and specifications for international haemiglobinocyanide standard (4th edition). J Clin Pathol 1996; 49: 271-4.
- 19Judkiewicz L, Bugala I, Bartosz G. Pink test' and osmotic fragility test for the diagnosis of hereditary spherocytosis: another view. Eur J Haematol 1989; 42: 217.
- 20Takebayashi J, Kaji H, Ichiyama K, et al. Inhibition of free radical-induced erythrocyte hemolysis by 2-O-substituted ascorbic acid derivatives. Free Radic Biol Med 2007; 43: 1156-64.
- 21 R: A Language and Environment for Statistical Computing. R foundation for statistical computing R core team, Vienna, Austria. 2016. [accessed 2018 april] Available from: https://www.r-project.org/.
- 22Wickham H. Ggplot2. 1st ed. New York, NY: Springer-Verlag; 2009.
- 23Endres-Dighe SM, Guo Y, Kanias T, et al. Blood, sweat and tears: red blood cell-Omics study objectives, design, and recruitment activities. Transfusion 2019; 59: 46-56.
- 24Gemelli CN, Hayman J, Waller D. Frequent whole blood donors: understanding this population and predictors of lapse. Transfusion 2017; 57: 108-14.
- 25Chansky MC, King MR, Bialkowski W, et al. Qualitative assessment of pica experienced by frequent blood donors. Transfusion 2017; 57: 946-51.
- 26Yazer MH, Delaney M, Germain M, et al. Biomedical excellence for safer transfusion C. Trends in US minority red blood cell unit donations. Transfusion 2017; 57: 1226-34.
- 27Yazer MH, Vassallo R, Delaney M, et al. Biomedical excellence for safer transfusion C. Trends in age and red blood cell donation habits among several racial/ethnic minority groups in the United States. Transfusion 2017; 57: 1644-55.
- 28Rigas AS, Sorensen CJ, Pedersen OB, et al. Predictors of iron levels in 14,737 Danish blood donors: results from the Danish blood donor study. Transfusion 2014; 54: 789-96.
- 29Bloch EM, Mast AE, Josephson CD, et al. Teenage blood donors: are we asking too little and taking too much? Pediatrics 2017; 139: e20162955.
- 30Kiss JE, Brambilla D, Glynn SA, et al. National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). Oral iron supplementation after blood donation: a randomized clinical trial. JAMA 2015; 313: 575-83.
- 31Mast AE, Bialkowski W, Bryant BJ, et al. A randomized, blinded, placebo-controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors. Transfusion 2016; 56: 1588-97.
- 32Mast AE, Blinder MA, Gronowski AM, et al. Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clin Chem 1998; 44: 45-51.
- 33Burns ER, Goldberg SN, Lawrence C, et al. Clinical utility of serum tests for iron deficiency in hospitalized patients. Am J Clin Pathol 1990; 93: 240-5.
- 34Kanias T, Sinchar D, Osei-Hwedieh D, et al. Testosterone-dependent sex differences in red blood cell hemolysis in storage, stress, and disease. Transfusion 2016; 56: 2571-83.
- 35Osei-Hwedieh DO, Kanias T, Croix CS, et al. Sickle cell trait increases red blood cell storage hemolysis and post-transfusion clearance in mice. EBioMedicine 2016; 11: 239-48.
- 36de Wolski K, Fu X, Dumont LJ, et al. Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells. Haematologica 2016; 101: 578-86.
- 37Chasse M, McIntyre L, English SW, et al. Effect of blood donor characteristics on transfusion outcomes: a systematic review and meta-analysis. Transfus Med Rev 2016; 30: 69-80.
- 38Chasse M, McIntyre L, Tinmouth A, et al. Clinical effects of blood donor characteristics in transfusion recipients: protocol of a framework to study the blood donor-recipient continuum. BMJ Open 2015; 5: e007412.
- 39Chasse M, Tinmouth A, English SW, et al. Association of blood donor age and sex with recipient survival after red blood cell transfusion. JAMA Intern Med 2016; 176: 1307-14.
- 40Edgren G, Ullum H, Rostgaard K, et al. Association of donor age and sex with survival of patients receiving transfusions. JAMA Intern Med 2017; 177: 854-60.
- 41Murphy MF. The epidemiology of transfusion: where blood goes and why we should care about it. Transfusion 2017; 57: 2821-3.
- 42Karafin MS, Bruhn R, Westlake M, et al. Demographic and epidemiologic characterization of transfusion recipients from four US regions: evidence from the REDS-III recipient database. Transfusion 2017; 57: 2903-13.
- 43Kleinman S, Busch MP, Murphy EL, et al. The national heart, lung, and blood institute recipient epidemiology and donor evaluation study (REDS-III): a research program striving to improve blood donor and transfusion recipient outcomes. Transfusion 2014; 54: 942-55.
- 44Mock DM, Matthews NI, Zhu S, et al. Red blood cell (RBC) survival determined in humans using RBCs labeled at multiple biotin densities. Transfusion 2011; 51: 1047-57.
- 45de Back DZ, Vlaar R, Beuger B, et al. A method for red blood cell biotinylation in a closed system. Transfusion 2018; 58: 896-904.
- 46Kanias T, Dennis CJ, Meyer EM, et al. Development of GMP protocol for the evaluation of biotinylated red blood cell recovery after transfusion. Transfusion 2017; 57: 170A-A.