Blood-storage duration affects hematological and metabolic profiles in patients with sickle cell disease receiving transfusions
Matthew S. Karafin, Abby L. Grier, Ross M. Fasano, Anton Ilich, David Wichlan, Ada Chang, Sonjile M. James, Hailly E. Butler, Oleg Kolupaev, Melissa C. Caughey, Daniel J. Stephenson, Julie A. Reisz, Nigel S. Key, Joshua J. Field, Jane A. Little, Steven L. Spitalnik, Angelo D’Alessandro
Matthew S. Karafin, Abby L. Grier, Ross M. Fasano, Anton Ilich, David Wichlan, Ada Chang, Sonjile M. James, Hailly E. Butler, Oleg Kolupaev, Melissa C. Caughey, Daniel J. Stephenson, Julie A. Reisz, Nigel S. Key, Joshua J. Field, Jane A. Little, Steven L. Spitalnik, Angelo D’Alessandro
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Clinical Research and Public Health Clinical Research Hematology

Blood-storage duration affects hematological and metabolic profiles in patients with sickle cell disease receiving transfusions

Abstract

BACKGROUND Patients with sickle cell disease (SCD) frequently receive RBC units stored near the end of their permissible storage duration. We aimed to determine whether RBC storage duration influences recipient hematological, metabolic, and clinical chemistry parameters.METHODS In a randomized, prospective, double-blind trial, 24 adults with SCD receiving chronic transfusion therapy were assigned to receive three consecutive outpatient transfusions with RBCs stored for either ≤10 days (short-stored; n = 13) or ≥30 days (long-stored; n = 11). Blood samples were collected from transfused units and from recipients at predefined time points for metabolomics, cytokine, and clinical laboratory analyses. The primary outcomes included post-transfusion hemoglobin and RBC count increments, metabolic markers of oxidative stress, iron metabolism, inflammation, and renal function.RESULTS Transfusion of short-stored RBCs was associated with significantly higher circulating 2,3-bisphosphoglycerate levels for up to 2 weeks after transfusion. Nadir RBC counts and hemoglobin A levels were higher in recipients of short-stored RBCs. In contrast, recipients of long-stored RBCs had higher transferrin saturation and plasma iron levels, elevated markers of oxidative stress and renal dysfunction, and increased proinflammatory cytokines and immunomodulatory metabolites. Metabolomics revealed storage age–dependent alterations in glycolysis, purine, and sphingolipid metabolism. Cytokine profiles and hematologic parameters corroborated the metabolic findings, indicating improved post-transfusion metabolic and inflammatory status with short-stored RBCs.CONCLUSION Transfusion of short-stored RBCs yielded favorable metabolic and hematologic outcomes in adults with SCD, independent of immediate clinical endpoints.TRIAL REGISTRATION ClinicalTrials.gov NCT03704922FUNDING National Heart, Lung, and Blood Institute (NHLBI), NIH (K23HL136787, R01HL148151, R01HL146442, and R01HL149714).

Authors

Matthew S. Karafin, Abby L. Grier, Ross M. Fasano, Anton Ilich, David Wichlan, Ada Chang, Sonjile M. James, Hailly E. Butler, Oleg Kolupaev, Melissa C. Caughey, Daniel J. Stephenson, Julie A. Reisz, Nigel S. Key, Joshua J. Field, Jane A. Little, Steven L. Spitalnik, Angelo D’Alessandro

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Figure 2

Metabolic effect of transfusion on the recipients’ RBC metabolome.

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Metabolic effect of transfusion on the recipients’ RBC metabolome. (A) ...
(A) Twenty-six patients with SCD received 3 consecutive transfusions with short-stored (<10 days) or long-stored (≥30) RBCs. RBC samples were drawn for metabolomics analysis of plasma and RBCs from the recipient at baseline, before transfusion, and 2 or 24 hours after each one of the transfusion events. Two patients were excluded from the long-stored RBC study arm because some of the units they received did not match the age criteria of the study protocol. (B–D) UMAP (B), LDA (C), and heatmap (D) of significant RBC metabolites by time and storage age of blood by LDA. (E) Line plot of temporal changes in 2,3-BPG over multiple transfusions as a function of the storage age of the blood (light red and dark red for short-stored and long-stored units, respectively).