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Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use.

Authors
  • Smethurst, Peter A1
  • Jolley, Jennifer1
  • Braund, Rebecca2
  • Proffitt, Sue1
  • Lynes, Thomas3
  • Hazell, Matthew3
  • Mellor, Phil2
  • Ridgwell, Kay4
  • Procter, Simon5
  • Griffiths, Alexandra6
  • Marinaki, Anthony M7
  • New, Helen V8, 9
  • Murphy, Gavin J10
  • Edmondson, Dave2
  • Cardigan, Rebecca1, 11
  • 1 Component Development Laboratory, NHS Blood and Transplant, Cambridge, United Kingdom. , (United Kingdom)
  • 2 Manufacturing & Development, NHS Blood and Transplant, Bristol, United Kingdom. , (United Kingdom)
  • 3 Red Cell Immunohaematology, NHS Blood and Transplant, Bristol, United Kingdom. , (United Kingdom)
  • 4 IBGRL Protein Development & Production Unit, NHS Blood and Transplant, Bristol, United Kingdom. , (United Kingdom)
  • 5 Quality Monitoring, NHS Blood and Transplant, London, United Kingdom. , (United Kingdom)
  • 6 Clinical Trials Unit, NHS Blood and Transplant, Bristol, United Kingdom. , (United Kingdom)
  • 7 Purine Research Laboratory, St Thomas' Hospital, London, United Kingdom. , (United Kingdom)
  • 8 Clinical Directorate, NHS Blood and Transplant, London, United Kingdom. , (United Kingdom)
  • 9 Department of Haematology, Imperial College London, London, United Kingdom. , (United Kingdom)
  • 10 Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, Glenfield General Hospital, University of Leicester, Leicester, United Kingdom. , (United Kingdom)
  • 11 Department of Haematology, University of Cambridge, Cambridge, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
Transfusion
Publication Date
Sep 01, 2019
Volume
59
Issue
9
Pages
2952–2963
Identifiers
DOI: 10.1111/trf.15426
PMID: 31294868
Source
Medline
Language
English
License
Unknown

Abstract

Rejuvenation of stored red blood cells (RBCs) increases levels of adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) to those of fresh cells. This study aimed to optimize and validate the US-approved process to a UK setting for manufacture and issue of rejuvenated RBCs for a multicenter randomized controlled clinical trial in cardiac surgery. Rejuvenation of leukoreduced RBC units involved adding a solution containing pyruvate, inosine, phosphate, and adenine (Rejuvesol, Zimmer Biomet), warming at 37°C for 60 minutes, then "manual" washing with saline adenine glucose mannitol solution. A laboratory study was conducted on six pools of ABO/D-matched units made the day after donation. On Days 7, 21, and 28 of 4 ± 2°C storage, one unit per pool was rejuvenated and measured over 96 hours for volume, hematocrit, hemolysis, ATP, 2,3-DPG, supernatant potassium, lactate, and purines added (inosine) or produced (hypoxanthine) by rejuvenation. Subsequently, an operational validation (two phases of 32 units each) was undertaken, with results from the first informing a trial component specification applied to the second. Rejuvenation effects were also tested on crossmatch reactivity and RBC antigen profiles. Rejuvenation raised 2,3-DPG to, and ATP above, levels of fresh cells. The final component had potassium and hemolysis values below those of standard storage Days 7 and 21, respectively, containing 1.2% exogenous inosine and 500 to 1900 μmoles/unit of hypoxanthine. The second operational validation met compliance to the trial component specification. Rejuvenation did not adversely affect crossmatch reactivity or RBC antigen profiles. The validated rejuvenation process operates within defined quality limits, preserving RBC immunophenotypes, enabling manufacture for clinical trials. © 2019 Crown copyright. Transfusion © 2019 AABB.

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