Short- and long-term effects of transfusion in β-thalassemia: a longitudinal study of transfusion efficiency factors

The complex interplay between donor and recipient factors likely influences transfusion outcomes in transfusion-dependent thalassemia (TDT). We investigated physiological responses to transfusion shortly after it and 1 week later, focusing on hemoglobin (Hb) increment (ΔHb) and its determinants, using longitudinal data from 36 patients with TDT and 58 red blood cell (RBC) units. Immediate anemia correction after transfusion was associated with decreases in platelets and nucleated RBCs, increases in ADAMTS13 antigen and plasma amino acid levels, and temporary rises in hemolysis and phthalates. One week after transfusion, at the peak of erythroid suppression, plasma antioxidants and mechanical hemolysis decreased, whereas proteasome activity at the RBC membrane increased. Leukocyte levels declined, markers of thrombotic risk and endothelium dysfunction improved, and hepcidin as well as plasma glutamine and deoxyadenosine, increased. In addition to female sex and anemia, ΔHb was influenced by recipient baseline monocyte levels, hypercoagulability, and plasma metabolites, such as methionine, adenosine, acyl-carnitines, and bile acids. Donor RBC unit factors, including residual platelet levels, RBC proteasome activity, arginine metabolism, and catecholamine content also had significant correlations. Notably, the baseline neutrophil-to-lymphocyte ratio strongly affected ΔHb soon after transfusion, after adjusting for confounders. At the 1-week mark, ΔHb correlated with storability markers, such as oxidative hemolysis and phthalates, which, to our knowledge, is a first-ever described connection. Importantly, the percentage of phosphatidylserine-exposing donor RBCs and the uric acid-dependent antioxidant capacity of the RBC units significantly influenced ΔHb at the 1-week time point. These findings enhance our understanding of transfusion dynamics, paving the way for more personalized and effective care strategies in TDT management.