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 7

Metabolic correlates to clinical chemistry and hematological parameters.

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Metabolic correlates to clinical chemistry and hematological parameters....
(A) Correlation matrix (Spearman’s rho) between metabolites and clinical chemistry and complete blood count parameters in transfusion recipients. (B) Same as in A, with the z axis representing Spearman’s rho positive versus negative values, and colors proportional to the –log10 P value of the correlation’s significance. (C and D) DSPC Networks 1 and 2 of the top metabolite-metabolite and metabolite-clinical covariates in this study. (E–G) Volcano plots (Spearman’s rho vs. –log10 P value for x and y axes, respectively) for clinical chemistry measurements of creatinine, hemoglobin (g/dL), and bilirubin in transfusion recipients. (H) Hive plot summarizing correlations (module of Spearman’s rho ≥0.85) for cytokines versus metabolites in RBC units, recipients’ RBCs, or plasma or clinical labs identifies a stronger association between proinflammatory cytokines and metabolites levels in patients with SCD who received units stored longer than 30 days. (I) Volcano plot of Spearman correlations to IL-6 levels in the recipient shows strong positive correlations among proinflammatory cytokines and circulating levels of kynurenine.