Marked Inter-Unit Variability and Early Depletion of 2,3-Diphosphoglycerate During Red Blood Cell Storage
6 affiliations
- 1Neurotraumatology and Neurosurgery Research Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
- 2Independent Researcher, 08035 Barcelona, Spain
- 3Department of Hematology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
- 4Blood and Tissue Bank, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
- 5Department of Surgery, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
- 6Department of Neurosurgery, Vall d’Hebron University Hospital, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Abstract
Red blood cell (RBC) transfusion aims to restore tissue oxygen delivery, yet a stored unit’s capacity to unload oxygen depends on 2,3-diphosphoglycerate (2,3-DPG), the principal allosteric modulator of hemoglobin–oxygen affinity. Randomized trials comparing fresher with older units have been consistently null, and all have used storage duration as the exposure variable. We asked whether storage age reflects the metabolic state of individual units. Twenty-four leukodepleted packed RBC units were sampled serially from day 3 to day 42 of standard cold storage. 2,3-DPG was quantified by liquid chromatography–mass spectrometry (LC–MS) with isotopically labelled internal standards, pH was measured in parallel, and trajectories were modelled by linear mixed effects with unit-level random intercepts. At day 3, 2,3-DPG spanned an approximately 18-fold range across units of identical age (0.8–14.7 µmol/g Hb; median 4.0): some were already near-depleted at the earliest sampled timepoint, while others retained near-physiological concentrations. This heterogeneity collapsed rapidly—median values fell to 20% of day-3 levels by day 7 and by more than 95% by day 14 (β = −0.298 µmol/g Hb per day, p < 0.001)—and were below the limit of detection in most units after day 17. pH declined monotonically to 6.40 ± 0.04 by day 42 (β = −0.0163 units per day, p < 0.001). Units of identical storage age therefore differ markedly in the levels of the metabolite that governs oxygen unloading, and are depleted long before the 42-day expiry limit, suggesting that storage duration alone may incompletely capture the metabolic state of stored red blood cell units.
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BibTeX
@article{peris2026marked,
title = {{Marked Inter-Unit Variability and Early Depletion of 2,3-Diphosphoglycerate During Red Blood Cell Storage}},
author = {Marta Peris and Juan Sahuquillo and Ana Ortuño and Verónica Pons and Marina Rierola and Maria A. Poca},
journal = {Cells},
year = {2026},
month = nov,
doi = {10.3390/cells15212028},
url = {https://www.mdpi.com/2073-4409/15/21/2028},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Marked Inter-Unit Variability and Early Depletion of 2,3-Diphosphoglycerate During Red Blood Cell Storage
AU - Marta Peris
AU - Juan Sahuquillo
AU - Ana Ortuño
AU - Verónica Pons
AU - Marina Rierola
AU - Maria A. Poca
PY - 2026
DA - 2026/11/06
JO - Cells
DO - 10.3390/cells15212028
UR - https://www.mdpi.com/2073-4409/15/21/2028
AB - Red blood cell (RBC) transfusion aims to restore tissue oxygen delivery, yet a stored unit’s capacity to unload oxygen depends on 2,3-diphosphoglycerate (2,3-DPG), the principal allosteric modulator of hemoglobin–oxygen affinity. Randomized trials comparing fresher with older units have been consistently null, and all have used storage duration as the exposure variable. We asked whether storage age reflects the metabolic state of individual units. Twenty-four leukodepleted packed RBC units were sampled serially from day 3 to day 42 of standard cold storage. 2,3-DPG was quantified by liquid chromatography–mass spectrometry (LC–MS) with isotopically labelled internal standards, pH was measured in parallel, and trajectories were modelled by linear mixed effects with unit-level random intercepts. At day 3, 2,3-DPG spanned an approximately 18-fold range across units of identical age (0.8–14.7 µmol/g Hb; median 4.0): some were already near-depleted at the earliest sampled timepoint, while others retained near-physiological concentrations. This heterogeneity collapsed rapidly—median values fell to 20% of day-3 levels by day 7 and by more than 95% by day 14 (β = −0.298 µmol/g Hb per day, p < 0.001)—and were below the limit of detection in most units after day 17. pH declined monotonically to 6.40 ± 0.04 by day 42 (β = −0.0163 units per day, p < 0.001). Units of identical storage age therefore differ markedly in the levels of the metabolite that governs oxygen unloading, and are depleted long before the 42-day expiry limit, suggesting that storage duration alone may incompletely capture the metabolic state of stored red blood cell units.
SN - 2073-4409
ER -