Addition of ascorbic acid solution to stored murine red blood cells increases posttransfusion recovery and decreases microparticles and alloimmunization

Authors

  • Sean R. Stowell,

    1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
    2. Puget Sound Blood Center Research Institute, Seattle, Washington
    3. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
    4. Department of Pathology, University of Pittsburgh and the Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
    Search for more papers by this author
    • SRS and NHS contributed equally to the work.
  • Nicole H. Smith,

    1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
    2. Puget Sound Blood Center Research Institute, Seattle, Washington
    3. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
    4. Department of Pathology, University of Pittsburgh and the Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
    Search for more papers by this author
    • SRS and NHS contributed equally to the work.
  • James C. Zimring,

    Corresponding author
    1. Puget Sound Blood Center Research Institute, Seattle, Washington
    2. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
    3. Department of Pathology, University of Pittsburgh and the Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
    • Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
    Search for more papers by this author
  • Xiaoyun Fu,

    1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
    2. Puget Sound Blood Center Research Institute, Seattle, Washington
    3. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
    4. Department of Pathology, University of Pittsburgh and the Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
    Search for more papers by this author
  • Andre F. Palmer,

    1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
    2. Puget Sound Blood Center Research Institute, Seattle, Washington
    3. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
    4. Department of Pathology, University of Pittsburgh and the Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
    Search for more papers by this author
  • Jorge Fontes,

    1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
    2. Puget Sound Blood Center Research Institute, Seattle, Washington
    3. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
    4. Department of Pathology, University of Pittsburgh and the Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
    Search for more papers by this author
  • Uddyalok Banerjee,

    1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
    2. Puget Sound Blood Center Research Institute, Seattle, Washington
    3. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
    4. Department of Pathology, University of Pittsburgh and the Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
    Search for more papers by this author
  • Mark H. Yazer

    1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
    2. Puget Sound Blood Center Research Institute, Seattle, Washington
    3. William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio
    4. Department of Pathology, University of Pittsburgh and the Institute for Transfusion Medicine, Pittsburgh, Pennsylvania
    Search for more papers by this author

Address reprint requests to: James C. Zimring, MD, PhD, Puget Sound Blood Center Research Institute, 1551 Eastlake Avenue E, Seattle, WA 98102; e-mail: jzimring@psbc.org.

Abstract

Background

The storage of red blood cells (RBCs) results in numerous changes, which over time result in decreased recovery of transfused RBCs. In addition (at least in animal models), stored RBCs can be more immunogenic and also stimulate the systemic release of inflammatory cytokines in transfusion recipients. One component of the RBC storage lesion is the accumulation of oxidative damage. We tested the hypothesis that adding a chemical antioxidant (ascorbic acid) to stored RBCs would improve the quality of the stored RBCs.

Study Design and Methods

RBCs were harvested from FVB.HOD mice that express an RBC-specific model transgene (HOD) and stored for 14 days with either ascorbic acid in saline or saline alone. Twenty-four-hour posttransfusion recovery of RBCs was tracked by flow cytometry. Alloimmunization was monitored by flow cytometry crossmatch. Cytokines were monitored by multiplex bead arrays.

Results

RBCs stored under standard conditions had decreased 24-hour posttransfusion recovery and increased induction of both alloantibodies and interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 secretion in the mouse recipients. Addition of ascorbic acid from 3.6 to 10.8 mmol/L resulted in a significant decrease in microparticle formation, an improved RBC 24-hour posttransfusion recovery (p < 0.01), and a decrease in recipient alloimmunization (p = 0.0001). Induction of MCP-1 and IL-6 secretion was not decreased by ascorbic acid.

Conclusions

These data indicate that the addition of ascorbic acid solution to RBCs during storage has a beneficial effect on recovery and immunogenicity of RBCs, but not cytokine induction. The addition of ascorbic acid (or other antioxidants) to human RBCs may have beneficial effects.

Ancillary