Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use.
2,3-Diphosphoglycerate
/ metabolism
Adenosine Triphosphate
/ blood
Blood Grouping and Crossmatching
Blood Loss, Surgical
/ prevention & control
Blood Preservation
/ methods
Cardiac Surgical Procedures
/ adverse effects
Cryopreservation
/ methods
Erythrocyte Count
Erythrocyte Transfusion
/ standards
Erythrocytes
/ cytology
Hemolysis
/ physiology
Humans
Immunophenotyping
Manufactured Materials
Purines
/ blood
Quality Control
Randomized Controlled Trials as Topic
Regenerative Medicine
/ methods
Rejuvenation
/ physiology
Journal
Transfusion
ISSN: 1537-2995
Titre abrégé: Transfusion
Pays: United States
ID NLM: 0417360
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
22
02
2019
revised:
01
05
2019
accepted:
10
06
2019
pubmed:
12
7
2019
medline:
10
6
2020
entrez:
12
7
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
STUDY DESIGN AND METHODS
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.
RESULTS
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.
CONCLUSION
The validated rejuvenation process operates within defined quality limits, preserving RBC immunophenotypes, enabling manufacture for clinical trials.
Substances chimiques
Purines
0
2,3-Diphosphoglycerate
138-81-8
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
2952-2963Subventions
Organisme : British Heart Foundation
ID : RG/13/6/29947
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/17/9/32812
Pays : United Kingdom
Investigateurs
Alan D Gray
(AD)
Matt Landrigan
(M)
Hardeep Aujla
(H)
Tracy Kumar
(T)
Marcin Wozniak
(M)
Tom Bullock
(T)
Renate Hodge
(R)
Alison Deary
(A)
Informations de copyright
© 2019 Crown copyright. Transfusion © 2019 AABB.
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