Hemolysis Pathways during Storage of Erythrocytes and Inter-Donor Variability in Erythrocyte Morphology

Melzak, Kathryn A.; Spouge, John L.; Boecker, Clemens; Kirschhöfer, Frank; Brenner‐Weiß, Gerald

doi:10.1159/000508711

Cited by 12 publications

(8 citation statements)

References 39 publications

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“…Inevitably, the initially discoid stored RBCs irreversibly transform into more rigid shapes, that are prone to lysis, mainly from middle storage onward ( Bardyn et al, 2017 ; Tzounakas et al, 2021b ). It was recently proposed that there are two hemolysis pathways related to distinct RBC morphological changes during storage ( Melzak et al, 2021 ). The first one implicates stomatocytes, which transform to spherocytes via endocytic vesiculation ( Reinhart and Chien, 1986 ), while the second implicates echinocytes which turn to spherocytes after shedding vesicles from their spikes ( Iglic et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Relationship Between Free and Vesicular Hemoglobin in Stored Red Blood Cell Units

et al. 2022

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Red blood cells (RBCs) release hemoglobin (Hb)-containing extracellular vesicles (EVs) throughout their lifespan in the circulation, and especially during senescence, by spleen-facilitated vesiculation of their membrane. During ex vivo aging under blood bank conditions, the RBCs lose Hb, both in soluble form and inside EVs that accumulate as a part of storage lesion in the supernatant of the unit. Spontaneous hemolysis and vesiculation are increasingly promoted by the storage duration, but little is known about any physiological linkage between them. In the present study, we measured the levels of total extracellular and EV-enclosed Hb (EV-Hb) in units of whole blood (n = 36) or packed RBCs stored in either CPDA-1 (n = 99) or in CPD-SAGM additive solution (n = 46), in early, middle, and late storage. The spectrophotometry data were subjected to statistical analysis to detect possible correlation(s) between storage hemolysis and EV-Hb, as well as the threshold (if any) that determines the area of this dynamic association. It seems that the percentage of EV-Hb is negatively associated with hemolysis levels from middle storage onward by showing low to moderate correlation profiles in all strategies under investigation. Moreover, 0.17% storage hemolysis was determined as the potential cut-off, above which this inverse correlation is evident in non-leukoreduced CPDA units. Notably, RBC units with hemolysis levels > 0.17% are characterized by higher percentage of nanovesicles (<100 nm) over typical microvesicles (100–400 nm) compared with the lower hemolysis counterparts. Our results suggest an ordered loss of Hb during RBC accelerated aging that might fuel targeted research to elucidate its mechanistic basis.

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Section: Discussionmentioning

confidence: 99%

Deciphering the Relationship Between Free and Vesicular Hemoglobin in Stored Red Blood Cell Units

et al. 2022

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“…Groups of high and low haemolysis samples were obtained from the QC laboratory as described for a previous work that analysed RBC morphology [11]. The QC laboratory identified low and high haemolysis samples each week for five weeks of its routine analysis.…”

Section: Methodsmentioning

confidence: 99%

Lipid ratios as a marker for red blood cell storage quality and as a possible explanation for donor gender differences in storage quality

et al. 2020

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Background and objectives Red blood cells that are stored for transfusions as red cell concentrates (RCCs) undergo changes during the storage period, culminating in the lysis of the cells. The goal of this work is to find markers that are linked to high haemolysis, in order to explain the inter-donor variability that is known to occur in storage quality, and also the known differences between RCCs from male and female donors. Materials and methods The relative amounts of lipids at the end of the storage period were compared for one group of low haemolysis samples (24 units, all ≤0Á15% haemolysis), and one group of high haemolysis samples (26 units, all ≥0Á5% haemolysis). Representative lipids were analysed from different lipid classes, including cholesterol, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin and ceramide. Whole membrane preparations were analysed with one mass spectrometry technique, and lipid extracts were analysed with a second mass spectrometry technique. Results The ratio of palmitoyl-oleoyl phosphatidylcholine (POPC) to sphingomyelin was different for the high and low haemolysis groups (P = 0Á0001) and for the RCCs from male and female donors (P = 0Á0009). The ratio of cholesterol to phospholipids showed only minimal links to haemolysis. Higher relative amounts of sphingomyelin were associated with lower haemolysis, and higher relative amounts of ceramides were associated with increased haemolysis. Conclusion The level of sphingomyelinase activity and the resulting ratio of sphingomyelin to POPC is proposed as a possible marker for RCC storage quality.

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“…In recent years, the literature has widely discussed the unit-tounit variability of PRBCs features (Tarasev et al, 2014(Tarasev et al, , 2015Sparrow, 2017;Barshtein et al, 2020b;Melzak et al, 2021). PRBCs from different units differ significantly depending on the donor, the condition of the collection and processing of blood, and the PRBC unit storage conditions.…”

Section: Unit-to-unit Variability Of Rbc Deformabilitymentioning

confidence: 99%

Deformability of Stored Red Blood Cells

2021

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Red blood cells (RBCs) deformability refers to the cells’ ability to adapt their shape to the dynamically changing flow conditions so as to minimize their resistance to flow. The high red cell deformability enables it to pass through small blood vessels and significantly determines erythrocyte survival. Under normal physiological states, the RBCs are attuned to allow for adequate blood flow. However, rigid erythrocytes can disrupt the perfusion of peripheral tissues and directly block microvessels. Therefore, RBC deformability has been recognized as a sensitive indicator of RBC functionality. The loss of deformability, which a change in the cell shape can cause, modification of cell membrane or a shift in cytosol composition, can occur due to various pathological conditions or as a part of normal RBC aging (in vitro or in vivo). However, despite extensive research, we still do not fully understand the processes leading to increased cell rigidity under cold storage conditions in a blood bank (in vitro aging), In the present review, we discuss publications that examined the effect of RBCs’ cold storage on their deformability and the biological mechanisms governing this change. We first discuss the change in the deformability of cells during their cold storage. After that, we consider storage-related alterations in RBCs features, which can lead to impaired cell deformation. Finally, we attempt to trace a causal relationship between the observed phenomena and offer recommendations for improving the functionality of stored cells.

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Hemolysis Pathways during Storage of Erythrocytes and Inter-Donor Variability in Erythrocyte Morphology

Cited by 12 publications

References 39 publications

Deciphering the Relationship Between Free and Vesicular Hemoglobin in Stored Red Blood Cell Units

Deciphering the Relationship Between Free and Vesicular Hemoglobin in Stored Red Blood Cell Units

Lipid ratios as a marker for red blood cell storage quality and as a possible explanation for donor gender differences in storage quality

Deformability of Stored Red Blood Cells

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