Ethnicity, sex, and age are determinants of red blood cell storage and stress hemolysis: results of the REDS-III RBC-Omics study.

Genetic polymorphisms in blood donors may contribute to donor-specific differences in the survival of red blood cells (RBCs) during cold storage and after transfusion. Genetic variability is anticipated to be high in donors with racial admixture from malaria endemic regions such as Africa and Asia. The purpose of this study was to test the hypothesis that donor genetic background, reflected by sex and self-reported ethnicity, significantly modulates RBC phenotypes in storage. High throughput hemolysis assays were developed and used to evaluate stored RBC samples from 11 115 African American, Asian, white, and Hispanic blood donors from 4 geographically diverse regions in the United States. Leukocyte-reduced RBC concentrate-derived samples were stored for 39 to 42 days (1-6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Male sex was strongly associated with increased susceptibility to all 3 hemolysis measures (P < .0001). African American background was associated with resistance to osmotic hemolysis compared with other racial groups (adjusted P < .0001). Donor race/ethnicity was also associated with extreme (>1%) levels of storage hemolysis exceeding US Food and Drug Administration regulations for transfusion (hemolysis >1% was observed in 3.51% of Asian and 2.47% of African American donors vs 1.67% of white donors). These findings highlight the impact of donor genetic traits on measures of RBC hemolysis during routine cold storage, and they support current plans for genome-wide association studies, which may help identify hereditable variants with substantive effects on RBC storage stability and possibly posttransfusion outcomes.

[1]  M. Gladwin,et al.  Nitric oxide, hemolysis, and the red blood cell storage lesion: interactions between transfusion, donor, and recipient , 2012, Transfusion.

[2]  M. Gladwin Revisiting the hyperhemolysis paradigm. , 2015, Blood.

[3]  M. Gladwin,et al.  Storage lesion in banked blood due to hemolysis-dependent disruption of nitric oxide homeostasis , 2009, Current opinion in hematology.

[4]  S. Singh,et al.  Decrease in Antioxidant Status of Plasma and Erythrocytes from Geriatric Population , 2012, Disease markers.

[5]  M. Gladwin,et al.  Assessing the influence of component processing and donor characteristics on quality of red cell concentrates using quality control data , 2016, Vox sanguinis.

[6]  H. Howie,et al.  Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells , 2016, Haematologica.

[7]  Carol West,et al.  Hematologic differences between African-Americans and whites: the roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. , 2005, Blood.

[8]  G. Bartosz,et al.  ‘PINK TEST’ AND OSMOTIC FRAGILITY TEST FOR THE DIAGNOSIS OF HEREDITARY SPHEROCYTOSIS: ANOTHER VIEW , 1989, European journal of haematology.

[9]  J. Hoebeke,et al.  Mechanisms of genetically-based resistance to malaria. , 2010, Gene.

[10]  W. Piyamongkol,et al.  Sensitivity and Specificity of Simple Erythrocyte Osmotic Fragility Test for Screening of Alpha-Thalassemia-1 and Beta-Thalassemia Trait in Pregnant Women , 2010, Gynecologic and Obstetric Investigation.

[11]  Ning Zhang,et al.  Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. , 2010, Blood.

[12]  B. Griffith,et al.  Plasma Protective Effect on Red Blood Cells Exposed to Mechanical Stress , 1997, ASAIO journal.

[13]  Janet S. Lee,et al.  Nitric Oxide Scavenging by Red Blood Cell Microparticles and Cell-Free Hemoglobin as a Mechanism for the Red Cell Storage Lesion , 2011, Circulation.

[14]  Janet S. Lee,et al.  Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice , 2016, EBioMedicine.

[15]  A. Forster,et al.  Association of Blood Donor Age and Sex With Recipient Survival After Red Blood Cell Transfusion. , 2016, JAMA internal medicine.

[16]  A. Forster,et al.  Effect of Blood Donor Characteristics on Transfusion Outcomes: A Systematic Review and Meta-Analysis. , 2016, Transfusion medicine reviews.

[17]  A. Tai,et al.  Inhibition of free radical-induced erythrocyte hemolysis by 2-O-substituted ascorbic acid derivatives. , 2007, Free radical biology & medicine.

[18]  H. Ullum,et al.  Association of Donor Age and Sex With Survival of Patients Receiving Transfusions , 2017, JAMA internal medicine.

[19]  M. Gladwin,et al.  Testosterone‐dependent sex differences in red blood cell hemolysis in storage, stress, and disease , 2016, Transfusion.

[20]  A. Zanella,et al.  A new test for the laboratory diagnosis of spherocytosis. , 1984, Acta haematologica.

[21]  E. Hod,et al.  Frequency of glucose‐6‐phosphate dehydrogenase–deficient red blood cell units in a metropolitan transfusion service , 2013, Transfusion.

[22]  J. Eikelboom,et al.  Red blood cell processing methods and in-hospital mortality: a transfusion registry cohort study. , 2016, The Lancet. Haematology.

[23]  J. Acker,et al.  Biopreservation of red blood cells – the struggle with hemoglobin oxidation , 2010, The FEBS journal.

[24]  S. Lewis,et al.  Recommendations for reference method for haemoglobinometry in human blood (ICSH standard 1995) and specifications for international haemiglobinocyanide standard (4th edition). , 1996, Journal of clinical pathology.

[25]  Donald J. McMahon,et al.  Prolonged red cell storage before transfusion increases extravascular hemolysis , 2017, The Journal of clinical investigation.

[26]  N. Mohandas,et al.  Osmotic gradient ektacytometry: comprehensive characterization of red cell volume and surface maintenance. , 1983, Blood.

[27]  Catherine Quantin,et al.  Effect of storage time and donor sex of transfused red blood cells on 1‐year survival in patients undergoing cardiac surgery: an observational study , 2016, Transfusion.

[28]  A. Seltsam,et al.  Menopausal status affects the susceptibility of stored RBCs to mechanical stress , 2011, Vox sanguinis.

[29]  E. Rubin,et al.  Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease. , 1997, Science.

[30]  I. Papassideri,et al.  Donor variation effect on red blood cell storage lesion: a multivariable, yet consistent, story , 2016, Transfusion.

[31]  S. Stowell,et al.  Strain‐specific red blood cell storage, metabolism, and eicosanoid generation in a mouse model , 2014, Transfusion.

[32]  R. Weinstein,et al.  Does a patient with hereditary spherocytosis qualify for preoperative autologous blood donation? , 1997, Transfusion.

[33]  J. Jhang,et al.  Acquired hemoglobin variants and exposure to glucose‐6‐phosphate dehydrogenase deficient red blood cell units during exchange transfusion for sickle cell disease in a patient requiring antigen‐matched blood , 2013, Journal of clinical apheresis.