Donor genetic and nongenetic factors affecting red blood cell transfusion effectiveness.
Pubmed ID: 34793330
Pubmed Central ID: PMC8765041
Journal: JCI insight
Publication Date: 01/11/2022
Affiliation: Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
MeSH Terms: Humans, Male, Adult, Female, Aged, Middle Aged, Blood Donors, Retrospective Studies, Erythrocyte Transfusion, Hemoglobins, Hemolysis, Glucosephosphate Dehydrogenase Deficiency
Grants: UL1 TR001863, 75N98019D00032, 75N91019D00032, 75N91019D00036, R01 HL126130
Authors: Busch MP, Gladwin MT, Qiao H, Mast AE, Custer B, Kleinman S, Cable RG, Page GP, Spencer BR, Roubinian NH, Reese SE, Plimier C, Fang F, Goel R, Harris B, Hendrickson JE, Kanias T, Sloan SR, Spitalnik SL, Hod EA
Cite As: Roubinian NH, Reese SE, Qiao H, Plimier C, Fang F, Page GP, Cable RG, Custer B, Gladwin MT, Goel R, Harris B, Hendrickson JE, Kanias T, Kleinman S, Mast AE, Sloan SR, Spencer BR, Spitalnik SL, Busch MP, Hod EA, National Heart Lung and Blood Institute (NHLBI) Recipient Epidemiology and Donor Evaluation Study IV Pediatrics (REDS-IV-P). Donor genetic and nongenetic factors affecting red blood cell transfusion effectiveness. JCI Insight 2022 Jan 11;7. (1).
BACKGROUNDRBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness.METHODSThis is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness.RESULTSBlood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, γ irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor G6PD deficiency and polymorphisms in SEC14L4, HBA2, and MYO9B genes were associated with decreased hemoglobin increments. Donor G6PD deficiency and polymorphisms in SEC14L4 were associated with increased transfusion requirements in the subsequent 48 hours.CONCLUSIONDonor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products.FUNDINGFunding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).