Metabolic impact of red blood cell exchange with rejuvenated red blood cells in sickle cell patients

摘要

BACKGROUND Red blood cell exchange (RCE) transfusions are a mainstay in the treatment of sickle cell anemia (SCA), and allow a temporary restoration of physiological parameters with respect to erythrocyte oxygen carrying capacity and systems metabolism. Recently, we noted that 1) RCE significantly impacts recipients' metabolism in SCA; 2) fresh and end‐of‐storage red blood cell (RBC) units differently impact systems of metabolism in healthy autologous recipients; and 3) phosphate/inosine/pyruvate/adenine (PIPA) solution reverses the metabolic age of stored RBCs. Therefore, we hypothesized that RCE with PIPA‐treated RBC units could further increase the metabolic benefits of RCE in SCA patients. STUDY DESIGN AND METHODS Circulating plasma and erythrocytes were collected from patients with SCA before and after RCE, with either conventional or PIPA‐treated RBC units, prior to metabolomics analyses. RESULTS Consistent with prior work, RCE significantly decreased circulating levels of markers of systemic hypoxemia (lactate, succinate) and decreased plasma levels of acyl‐carnitines and amino acids. However, PIPA‐treated exchanges were superior to untreated RCEs, with a higher energy state and an increased capacity to activate the pentose phosphate pathway and glutamine metabolism. In addition, RBCs and plasma from recipients of PIPA‐treated RBC units resulted in significantly decreased levels of post‐transfusion plasticizers, though at the expense of higher circulating levels of oxidized purines (hypoxanthine, xanthine, and the antioxidant urate). CONCLUSION Transfusion of PIPA‐treated RBCs further increases the metabolic benefits of RCE to patients with SCA, significantly reducing the levels of post‐transfusion plasticizers.