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
View: Text | PDF
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

×

Figure 1

Blood units stored longer than 30 days are metabolically distinct from units stored less than 10 days.

Options: View larger image (or click on image) Download as PowerPoint
Blood units stored longer than 30 days are metabolically distinct from u...
(A) overview of the experimental design. Numbers indicate the total units transfused per transfusion event (Tx1–Tx3). (B) UMAP of metabolomics data for all blood units transfused at any of the 3 transfusion events for units stored for less than 10 days (short-stored) or longer than 30 days (long-stored). (C) As per the study design, the age of the blood, but not the transfusion sequence, was associated with significant metabolic changes (2-way ANOVA). The transfusion event sequence is shown merely to confirm the reproducibility of storage-age–related effects across events. (D) ROC curves for RBC and supernatant levels of the metabolic markers of the storage lesion (14) discriminant between short-stored and long-stored units. (E) Heatmap of the most significant metabolic changes in RBCs and supernatants as a function of the storage age of the unit (2-way ANOVA). (F) Summary overview of the RBC storage metabolic lesion. Illustration was created with BioRender.com.