Impact of Aged Stored Red Blood Cells on the Human Plasma Metabolome

Background: Red blood cell (RBC) transfusion is a critical therapeutic intervention in managing anemia, surgical blood loss, and trauma. However, prolonged storage of RBCs induces metabolic, structural, and biochemical changes, collectively known as the “storage lesion.” These changes may affect the plasma metabolome post-transfusion, potentially leading to adverse outcomes. Aim: This study aimed to evaluate the effects of aged, stored RBCs on the human plasma metabolome, focusing on metabolic changes and their clinical implications. Methods: A prospective observational study was conducted with 100 participants who received RBC transfusions. Participants were categorized into three groups based on RBC storage duration: <14 days, 14–28 days, and >28 days. Plasma samples were collected pre-transfusion, and at 24 and 72 hours post-transfusion, and analyzed using advanced metabolomic techniques. Key parameters, including hemoglobin levels, plasma lactate, potassium was measured. Statistical analysis was performed using SPSS version 23.0, with a significance threshold of p<0.05. Results: Plasma lactate levels significantly increased post-transfusion across all groups, with the highest levels observed in the >28 days group (mean: 3.2 mmol/L at 24 hours). Plasma potassium levels also showed a marked increase, with levels peaking at 5.8 mmol/L in the >28 days group. Hemoglobin levels increased uniformly in all groups, confirming effective oxygen-carrying capacity restoration. Statistical analysis revealed significant differences in plasma metabolite levels between groups, particularly between the <14 days and >28 days groups (p<0.001). Conclusion: Aged stored RBCs induce significant metabolic changes in the plasma metabolome, particularly elevated lactate, and potassium levels. While hemoglobin levels remained unaffected, the findings highlight the potential metabolic stress associated with transfusing older RBCs. Recommendations: To mitigate the risks associated with aged stored RBCs, it is recommended to prioritize fresher RBCs for vulnerable populations and explore interventions to minimize storage-induced metabolic alterations. Further research is warranted to establish clinical thresholds for RBC storage durations.