Real Age: Red Blood Cell Aging During Storage

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.

Deformability based sorting of stored red blood cells reveals donor-dependent aging curves

“…RBC deformability is a key part of the mechanism for splenic clearance of RBCs 50,51 , and has therefore been frequently proposed as a potential biomarker for estimating the clearance time of transfused RBCs 52,53 . Traditional methods, such as ektacytometry 28,29,54,55 , test the rheological properties of RBC derived from bulk flow, which does not correlate well with circulatory clearance time 56,57 .…”

Ethyl glucuronide, a marker of alcohol consumption, correlates with metabolic markers of oxidant stress but not with hemolysis in stored red blood cells from healthy blood donors

“…While these events have been observed in all laboratory studies on the storage lesion to date, the rate and extent of the progression of the so‐called storage lesion appears to be dependent on donor‐to‐donor variability in the capacity to cope with oxidant stress . As such, we now appreciate that the metabolic age of a unit of blood is qualitatively different from its chronological age, that is, the amount of time elapsed since the day of donation . Significant heterogeneity is indeed observed across donors with respect to storage quality markers such as hemolysis and posttransfusion recovery in healthy autologous volunteers in humans and rodent models of storage and transfusion .…”

The Contribution of Storage Medium and Membranes in the Microwave Dielectric Response of Packed Red Blood Cells Suspension

“…During cold storage, PRBCs undergo slow detrimental changes that are collectively termed storage lesion [1][2][3]. Aging-related processes (that are at least partially due to the sensitivity of cells to oxidative stress [4]) lead to significant metabolic and structural changes in red blood cells [5][6][7][8], and involve global biochemical and biophysical alteration, remodeling of the cell membrane, and cytoplasm composition [3,9]. The most studied changes include: adenosine triphosphate (ATP) and 2,3-bisphosphoglycerate (2.3-DPG) depletion [9], loss of cellular antioxidant capability [10,11], changes in K+ and Na+ concentration [12,13], loss of membrane and skeleton proteins [14,15], loss of membrane lipids, and changes in their in/out distribution, vesicle generation [16,17], oxidation and 2 of 9 remodeling of skeleton proteins [18], clustering of band 3 proteins [19,20], alteration of nitric oxide signaling [21,22], decrease in antioxidant activity [23][24][25], etc.…”