Abstract
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).
Highlights
RBC transfusions can be a critical life-saving intervention for hospitalized and chronically transfused patients
We identified 46,705 and 5354 patients, with 102,043 and 6168 evaluable single RBC unit transfusion episodes, in the full cohort and the RBC-Omics Study subset [19], respectively; this allowed for examining the hemoglobin increment as an outcome (Figure 1)
We explored the effects of other donor single nucleotide polymorphisms (SNPs) on transfusion effectiveness, as defined by the recipient hemoglobin increment, in our multivariable model adjusting for donor, component, and recipient factors
Summary
RBC transfusions can be a critical life-saving intervention for hospitalized and chronically transfused patients. Blood donors are a heterogenous population for which biologic, genetic, and behavioral variables interact with various manufacturing and storage conditions to contribute to variation in the hemoglobin dose of packed RBC units and their responses to cold storage. Intravascular hemolysis may affect kidney function and exacerbate other human diseases [7, 8]. Because these laboratory values are often measured in hospitalized patients requiring transfusion, we assessed transfusion effectiveness by the change in hemoglobin, bilirubin, or creatinine levels following transfusion. 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
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