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

Transfusion. 2019 Oct;59(10):3102-3112. doi: 10.1111/trf.15467. Epub 2019 Aug 5.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anemia, Sickle Cell / metabolism
  • Anemia, Sickle Cell / therapy*
  • Erythrocyte Transfusion / methods*
  • Erythrocytes / metabolism
  • Exchange Transfusion, Whole Blood
  • Humans
  • Male
  • Metabolomics
  • Pentose Phosphate Pathway
  • Plasticizers / metabolism
  • Purines / metabolism

Substances

  • Plasticizers
  • Purines
  • purine