Measuring Post-transfusion Recovery and Survival of Red Blood Cells: Strengths and Weaknesses of Chromium-51 Labeling and Alternative Methods

Abstract

The proportion of transfused red blood cells (RBCs) that remain in circulation is an important surrogate marker of transfusion efficacy and contributes to predict the potential benefit of a transfusion process. Over the last 50 years, most of the transfusion recovery data were generated by chromium-51 (51Cr)-labeling studies and were predominantly performed to validate new storage systems and new processes to prepare RBC concentrates. As a consequence, our understanding of transfusion efficacy is strongly dependent on the strengths and weaknesses of 51Cr labeling in particular. Other methods such as antigen mismatch or biotin-based labeling can bring relevant information, for example, on the long-term survival of transfused RBC. These radioactivity-free methods can be used in patients including from vulnerable groups. We provide an overview of the methods used to measure transfusion recovery in humans, compare their strengths and weaknesses, and discuss their potential limitations. Also, based on our understanding of the spleen-specific filtration of damaged RBC and historical transfusion recovery data, we propose that RBC deformability and morphology are storage lesion markers that could become useful predictors of transfusion recovery. Transfusion recovery can and should be accurately explored by more than one method. Technical optimization and clarification of concepts is still needed in this important field of transfusion and physiology.

Hypoxic storage of red blood cells improves metabolism and post‐transfusion recovery

“…Hemolysis was treated in a combined fashion, owing to the lack of significant differences between the two conditions. Consistent with older reports, the high‐energy phosphate compound ATP had moderate but significant correlation to PTR (Fig. A).…”

Impact of taurine on red blood cell metabolism and implications for blood storage

“…However, it is worthwhile to point out that end of storage PTR in taurine‐supplemented FVB RBCs were still well below the 75% threshold, suggesting that the benefits associated with taurine supplementation in RBCs from this mouse strain, although robust and reproducible over multiple independent experiments, are not sufficient to normalize (compared to other mouse strains) the redox metabolism of stored RBCs from these mice. These results were accompanied by the observation of a beneficial impact on metabolic markers of PTR (ATP, GSH, hypoxanthine, 5‐HETE) in stored human RBCs when taurine was supplemented to storage additives. To this end, it is worth noting that PTR has been recently critiqued owing to several limitations associated with this assay, among which is the washing steps to remove the excess 51 Cr that may untimely remove the most damaged RBCs (a step that is not necessary in the mouse studies described in the present paper) or the questionable relevance of an assay that relies on healthy autologous volunteers instead of sick heterologous recipients.…”

Human platelets labeled at two discrete biotin densities are functional in vitro and are detected in vivo in the murine circulation: A promising approach to monitor platelet survival in vivo in clinical research

“…A major advantage of Bio labeling is that more than one PLT population can be tracked concurrently in vivo in the same recipient by labeling at more than one Bio density; this is well established for RBCs 20,28 . The different populations are monitored by ex vivo flow cytometry (FC) using streptavidin coupled to a detector molecule such as a fluorochrome.…”