Matthew Karafin published the initial results of his prospective randomized clinical trial in JCI.
Authors: Matthew S. Karafin, Abby S. Grier, Ross M. Fasano, Anton Ilich, David Wichlan, Ada Chang, Sonjile M. James, Hailly E. Butler, Oleg Kolupaev, Melissa C. Caughey, Daniel Stephenson, Julie A. Reisz, Nigel S. Key, Joshua J. Field, Jane A. Little, Steven L. Spitanik, Angelo D’Alessandro.
Citation: 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 A. Blood-storage duration affects hematological and metabolic profiles in patients with sickle cell disease receiving transfusions. J Clin Invest. 2025 Jul 3:e192920. doi: 10.1172/JCI192920. Epub ahead of print. PMID: 40608427.
Summary of findings:
Patients with sickle cell disease (SCD) frequently receive red blood cell (RBC) units stored near the end of their permissible storage life. To evaluate whether storage duration influences recipient metabolism, clinical chemistry and hematological parameters, we conducted a prospective, randomized, blinded trial comparing transfusions of RBC units stored for ≤10 days versus ≥30 days. Chronically transfused adults with SCD (N=24) received three consecutive outpatient transfusions with randomized-age RBCs, and blood samples from units and recipients were analyzed by metabolomics and clinical chemistry. Transfusion of short-stored units resulted in significantly higher circulating levels of 2,3-bisphosphoglycerate, an essential regulator of oxygen unloading, up to two weeks post-transfusion. Conversely, transfusions of long-stored RBCs were associated with lower hemoglobin and RBC increments, higher iron and transferrin saturation, pro-inflammatory cytokines and metabolites, oxidative stress and markers of renal dysfunction. Plasma and RBC metabolomic profiles revealed time- and storage-age-dependent alterations, particularly affecting glycolysis, purine, and sphingolipid metabolism. Transfusion of long-stored RBCs consistently worsened laboratory surrogates of oxygen delivery and RBC efficacy, and increased the circulating levels of immunomodulatory metabolites and pro-inflammatory cytokines. These findings highlight metabolic and hematologic advantages associated with transfusing fresher RBCs in adults with SCD. The additional relationships between storage duration and key clinical outcomes from this same clinical trial has just been accepted for publication in Blood RCI.