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    • To prevent the negative impact

    2018-10-23

    To prevent the negative impact of hemolysis, the U.S. Food and Drug Administration set the upper threshold of hemolysis in a RBC unit to be transfused at 1% but some RBC units stored under standard blood banking conditions fail to meet this requirement due to factors that may be donor specific (Mishler et al., 1979; Dumont and AuBuchon, 2008). The human HbAS RBCs purchased from a commercial blood bank for this study would not have met the regulatory requirement near the end of the FDA accepted shelf-life of 42days, as these units exhibited a hemolysis level of >1%. Other occult genetic mutations such as sickle cell trait that increase storage hemolysis may explain why some RBCs age faster during storage. The enhanced tissue sequestration of HbAS RBCs that we observed may be due to reduced deformability of HbAS RBC membrane that worsens during storage and increases the propensity for microvascular obstruction. However, splenectomy of recipient mice did not alter post-transfusion recovery of stored m-HbAS RBC. This observation is likely due to the fact that the liver is significantly larger and about ten times the cam kinase ii weight in mice, so that increases in circulating RBCs after splenectomy are not measurable (Sisto et al., 2003). The limitation in our technique to fully quantify the capacity of the liver to entrap and clear large numbers of stored RBCs in real time may account for the lack of observable differences. One limitation of this study and previous studies utilizing murine RBCs to study the effect of storage lesion on RBC post-transfusion survival is the number of mice that are needed to obtain sufficient volumes (~75ml) for conventional storage in pediatric transfer bags with diethylhexyl phthalate (DEHP). It has also been shown that storage in pediatric transfer bags increases RBC hemolysis and alters osmotic fragility (Kanias et al., 2013). These considerations demonstrate the practical challenges of an acceptable storage model to mimic RBC behavior in standard-sized blood bags. Of note, studies performed decades ago to determine the transfusion suitability of stored h-HbAS RBCs were not under current approved conditions (Levin and Truax, 1960; Ray et al., 1959). Nonetheless, murine RBCs stored under similar conditions exhibited progressive reduction in 24h post-transfusion survival with 64% post-transfusion survival following 14-day storage as well as phosphatidylserine externalization and reduced CD47 expression similar to trends observed in human RBCs at the end of 42-day storage (Gilson et al., 2009).
    Conflict of Interest Statement
    Authorship Contribution
    Acknowledgements This work was also partially supported by NIH grant HL058091 (DKS). Center for Biological Imaging is supported by NIH grant P01HL114453 and 1S10 OD019973. We would like to thank Christina Morse and Dr. Prabir Ray for their assistance with immunohistochemical staining of F4/80+ cells.
    Introduction The diagnosis of MS is often challenging, causing frequent errors or delays (Solomon et al., 2016). There is no single test that is performed to diagnose the disease; rather, the diagnostic process involves physical and neurological examinations, multiple MRIs, and a 6-month to 2-year time frame prior to final diagnosis, (Polman et al., 2011) which even then may be a “soft” diagnosis. Collectively, the exhaustive process of diagnosing (or ruling out) MS is costly and can adversely affect the patient as MS therapies may delayed during the diagnosing process. A simple, objective bloodstream-based biomarker remains an unmet clinical need (Polman et al., 2011). There have been recent reports of blood-based diagnostics in the literature, although these tests have suffered from either small patient numbers or very low diagnostic sensitivity. Here, we evaluate the performance of a blood-based lab test in distinguishing subjects with MS compared to subjects with other, non-MS neurologic disease (ONDs) and healthy controls. Specifically, we determined the amount of exogenously added C-peptide bound to a sample of erythrocytes (ERYs) obtained from the whole blood of people with MS to ERYs of healthy controls and controls with ONDs.