Effects of blood storage age on immune, coagulation, and nitric oxide parameters in transfused patients undergoing cardiac surgery
Philip C. Spinella
Department of Pediatrics, Washington University School of Medicine in St. Louis, Saint Louis, Missouri
Search for more papers by this authorRoman M. Sniecinski
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia
Search for more papers by this authorFelicia Trachtenberg
New England Research Institutes, Watertown, Massachusetts
Search for more papers by this authorHeather C. Inglis
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorGayatri Ranganathan
New England Research Institutes, Watertown, Massachusetts
Search for more papers by this authorJohn W. Heitman
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorFania Szlam
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia
Search for more papers by this authorAli Danesh
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorMars Stone
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorSheila M. Keating
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorJerrold H. Levy
Department of Anesthesiology and Critical Care, Duke University School of Medicine, Durham, North Carolina
Search for more papers by this authorSusan F. Assmann
New England Research Institutes, Watertown, Massachusetts
Search for more papers by this authorMarie E. Steiner
Department of Hematology and Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Search for more papers by this authorAllan Doctor
Department of Pediatrics, Washington University School of Medicine in St. Louis, Saint Louis, Missouri
Search for more papers by this authorCorresponding Author
Philip J. Norris
Vitalant Research Institute, San Francisco, California
Department of Laboratory Medicine, University of California, San Francisco, California
Department of Medicine, University of California, San Francisco, California
Address reprint requests to: Philip Norris, MD, Vitalant Research Institute, 270 Masonic Avenue, San Francisco, CA 94118; e-mail: [email protected].Search for more papers by this authorPhilip C. Spinella
Department of Pediatrics, Washington University School of Medicine in St. Louis, Saint Louis, Missouri
Search for more papers by this authorRoman M. Sniecinski
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia
Search for more papers by this authorFelicia Trachtenberg
New England Research Institutes, Watertown, Massachusetts
Search for more papers by this authorHeather C. Inglis
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorGayatri Ranganathan
New England Research Institutes, Watertown, Massachusetts
Search for more papers by this authorJohn W. Heitman
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorFania Szlam
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia
Search for more papers by this authorAli Danesh
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorMars Stone
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorSheila M. Keating
Vitalant Research Institute, San Francisco, California
Search for more papers by this authorJerrold H. Levy
Department of Anesthesiology and Critical Care, Duke University School of Medicine, Durham, North Carolina
Search for more papers by this authorSusan F. Assmann
New England Research Institutes, Watertown, Massachusetts
Search for more papers by this authorMarie E. Steiner
Department of Hematology and Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Search for more papers by this authorAllan Doctor
Department of Pediatrics, Washington University School of Medicine in St. Louis, Saint Louis, Missouri
Search for more papers by this authorCorresponding Author
Philip J. Norris
Vitalant Research Institute, San Francisco, California
Department of Laboratory Medicine, University of California, San Francisco, California
Department of Medicine, University of California, San Francisco, California
Address reprint requests to: Philip Norris, MD, Vitalant Research Institute, 270 Masonic Avenue, San Francisco, CA 94118; e-mail: [email protected].Search for more papers by this authorAbstract
BACKGROUND
Retrospective studies suggested that storage age of RBCs is associated with inflammation and thromboembolism. The Red Cell Storage Duration Study (RECESS) trial randomized subjects undergoing complex cardiac surgery to receive RBCs stored for shorter versus longer periods, and no difference was seen in the primary outcome of change in multiple organ dysfunction score.
STUDY DESIGN AND METHODS
In the current study, 90 subjects from the RECESS trial were studied intensively using a range of hemostasis, immunologic, and nitric oxide parameters. Samples were collected before transfusion and on Days 2, 6, 28, and 180 after transfusion.
RESULTS
Of 71 parameters tested, only 4 showed a significant difference after transfusion between study arms: CD8+ T-cell interferon-γ secretion and the concentration of extracellular vesicles bearing the B-cell marker CD19 were higher, and plasma endothelial growth factor levels were lower in recipients of fresh versus aged RBCs. Plasma interleukin-6 was higher at Day 2 and lower at Days 6 and 28 in recipients of fresh versus aged RBCs. Multiple parameters showed significant modulation after surgery and transfusion. Most analytes that changed after surgery did not differ based on transfusion status. Several extracellular vesicle markers, including two associated with platelets (CD41a and CD62P), decreased in transfused patients more than in those who underwent surgery without transfusion.
CONCLUSIONS
Transfusion of fresh versus aged RBCs does not result in substantial changes in hemostasis, immune, or nitric oxide parameters. It is possible that transfusion modulates the level of platelet-derived extracellular vesicles, which will require study of patients randomly assigned to receipt of transfusion to define.
CONFLICT OF INTEREST
The authors have disclosed no conflicts of interest.
Supporting Information
| Filename | Description |
|---|---|
| TRF_15228_Sup-0001-Figure_S1.docxWord 2007 document , 14.7 KB | Fig. S1: Coagulation factors that did not change significantly after transfusion. The mean level of coagulation factors and clotting parameters that showed no statistically significant differences over time in recipients of fresh versus standard aged blood are shown on Days 0, 2, 6, and 28 after transfusion. Factor levels are reported as a percentage of normal control plasma levels. Error bars represent standard error of the mean. ETP = endogenous thrombin potential; FM = fibrin monomer; PC = protein C; PH = peak thrombin; PTT = partial thromboplastin time; TFPI = tissue factor pathway inhibitor; TM = thrombomodulin; TPA = tissue plasminogen activator. |
| TRF_15228_MARS Supplemental figures 20180628.pptxWord 2007 document , 257.6 KB | Fig S2: Cellular immune factors and cytokines that did not change significantly after transfusion. (A) Cytokine levels were determined by a multiplex bead-based assay. Cytokines that showed a decrease from Day 0 to Day 2 after transfusion are shown on Days 0, 2, 6, and 28 after transfusion. (B) The mean levels of T cells that proliferate after anti-CD3/CD28 antibody stimulation (CFSElow), Treg cells, CD4+ T cells that secreted IL-17A, and CD8+ T cells that secreted IFN-γ after PMA/ionomycin stimulation are shown on Days 0, 6, 28, and 180 after transfusion. Cells were gated on lymphocytes based on FSC/SSC and live cells by viability staining. Treg cells were defined as the percentage of CD4+ T cells that were positive for CD25 and Foxp3. The percentage of CD4+ or CD8+ T cells positive for IL-17A or IFN-γ were calculated after subtracting background secretion of the cytokine by unstimulated control PBMCs. PDGF = platelet derived growth factor; sICAM = soluble intercellular adhesion molecule; MIP-1α = CCL3; sVCAM = soluble vascular cell adhesion molecule. *p < 0.05 comparing treatment arms at noted time point. |
| TRF_15228_Sup-0001-Figure_S1.docxWord 2007 document , 14.7 KB | Fig. S3: Extracellular vesicles bearing markers of their cell of origin and NO measures that did not change significantly after transfusion. The mean level of analytes that showed no statistically significant differences over time in recipients of fresh vs. standard aged blood are shown on Days 0, 2, 6, and 28 after transfusion. (A) EVs bearing markers of their cell of origin are shown. Only CD19+ EVs differed between the fresh and aged RBC arms. (B) NO parameters in recipient RBC samples are shown, none of which changed significantly over time. Error bars represent standard error of the mean |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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