Colleen G Koch1, Andra I Duncan2, Priscilla Figueroa3, Lu Dai4, Daniel I Sessler5, Steven M Frank6, Paul M Ness7, Tomislav Mihaljevic8, Eugene H Blackstone9. 1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medicine, Baltimore, Maryland. Electronic address: ckoch11@jhmi.edu. 2. Department of Cardiothoracic Anesthesiology, Cleveland Clinic, Cleveland, Ohio. 3. Department of Clinical Pathology, Cleveland Clinic, Cleveland, Ohio. 4. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, Ohio. 5. Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio. 6. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medicine, Baltimore, Maryland. 7. Department of Transfusion Medicine, Johns Hopkins Medicine, Baltimore, Maryland. 8. Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio. 9. Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio; Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.
Abstract
BACKGROUND: During cold storage, some red blood cell (RBC) units age more rapidly than others. Yet, the Food and Drug Administration has set a uniform storage limit of 42 days. Objectives of this review are to present evidence for an RBC storage lesion and suggest that functional measures of stored RBC quality-which we call real age-may be more appropriate than calendar age. METHODS: During RBC storage, biochemical substances and byproducts accumulate and RBC shape alters. Factors that influence the rate of degradation include donor characteristics, bio-preservation conditions, and vesiculation. Better understanding of markers of RBC quality may lead to standardized, quantifiable, and operationally practical measures to improve donor selection, assess quality of an RBC unit, improve storage conditions, and test efficacy of the transfused product. RESULTS: The conundrum is that clinical trials of younger versus older RBC units have not aligned with in vitro aging data; that is, the units transfused were not old enough. In vitro changes are considerable beyond 28 to 35 days, and average storage age for older transfused units was 14 to 21 days. CONCLUSIONS: RBC product real age varies by donor characteristics, storage conditions, and biological changes during storage. Metrics to measure temporal changes in quality of the stored RBC product may be more appropriate than the 42-day expiration date. Randomized trials and observational studies are focused on average effect, but, in the evolving age of precision medicine, we must acknowledge that vulnerable populations and individuals may be harmed by aging blood.
BACKGROUND: During cold storage, some red blood cell (RBC) units age more rapidly than others. Yet, the Food and Drug Administration has set a uniform storage limit of 42 days. Objectives of this review are to present evidence for an RBC storage lesion and suggest that functional measures of stored RBC quality-which we call real age-may be more appropriate than calendar age. METHODS: During RBC storage, biochemical substances and byproducts accumulate and RBC shape alters. Factors that influence the rate of degradation include donor characteristics, bio-preservation conditions, and vesiculation. Better understanding of markers of RBC quality may lead to standardized, quantifiable, and operationally practical measures to improve donor selection, assess quality of an RBC unit, improve storage conditions, and test efficacy of the transfused product. RESULTS: The conundrum is that clinical trials of younger versus older RBC units have not aligned with in vitro aging data; that is, the units transfused were not old enough. In vitro changes are considerable beyond 28 to 35 days, and average storage age for older transfused units was 14 to 21 days. CONCLUSIONS: RBC product real age varies by donor characteristics, storage conditions, and biological changes during storage. Metrics to measure temporal changes in quality of the stored RBC product may be more appropriate than the 42-day expiration date. Randomized trials and observational studies are focused on average effect, but, in the evolving age of precision medicine, we must acknowledge that vulnerable populations and individuals may be harmed by aging blood.
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