Blood-storage duration affects hematological and metabolic profiles in patients with sickle cell disease receiving transfusions. J Clin Invest 2025 Sep 02;135(17)
Date
07/03/2025Pubmed ID
40608427Pubmed Central ID
PMC12404753DOI
10.1172/JCI192920Scopus ID
2-s2.0-105015049134 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
BACKGROUNDPatients 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.METHODSIn 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.RESULTSTransfusion 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.CONCLUSIONTransfusion of short-stored RBCs yielded favorable metabolic and hematologic outcomes in adults with SCD, independent of immediate clinical endpoints.TRIAL REGISTRATIONClinicalTrials.gov NCT03704922FUNDINGNational Heart, Lung, and Blood Institute (NHLBI), NIH (K23HL136787, R01HL148151, R01HL146442, and R01HL149714).
Author List
Karafin MS, Grier AL, Fasano RM, Ilich A, Wichlan D, Chang A, James SM, Butler HE, Kolupaev O, Caughey MC, Stephenson DJ, Reisz JA, Key NS, Field JJ, Little JA, Spitalnik SL, D'Alessandro AAuthor
Joshua J. Field MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnemia, Sickle Cell
Blood Preservation
Cytokines
Double-Blind Method
Erythrocyte Transfusion
Female
Humans
Male
Metabolome
Middle Aged
Oxidative Stress
Prospective Studies
Time Factors
