Platelet vesicles are potent inflammatory mediators in red blood cell products and washing reduces the inflammatory phenotype

Almizraq, Ruqayyah J.; Kipkeu, Betty J; Acker, Jason P.

doi:10.1111/trf.15590

Cited by 9 publications

(10 citation statements)

References 71 publications

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“…Irrespective of RBC shape recovery, however, patients may still benefit from the removal of harmful mediators contained in the RBC storage supernatant by washing. [42][43][44][45] Our study further showed that SE/S cells were the only morphologic class of RBCs that were irreversibly damaged by storage. Our previous work and current findings suggest that SE/S cells undergo lysis readily, even upon relatively minor perturbations such as medium exchange with isotonic or slightly hypotonic saline 17 and conventional centrifugation.…”

Section: Discussionsupporting

confidence: 58%

“…If a similar level of shape recovery also occurs once stored RBCs are transfused into the body of the recipient, the resulting effect on blood rheology could potentially mitigate the negative effects of impaired RBC deformability typically associated with storage lesion. Irrespective of RBC shape recovery, however, patients may still benefit from the removal of harmful mediators contained in the RBC storage supernatant by washing 42–45 . Our study further showed that SE/S cells were the only morphologic class of RBCs that were irreversibly damaged by storage.…”

Section: Discussionmentioning

confidence: 58%

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Dynamics of shape recovery by stored red blood cells during washing at the single cell level

Shevkoplyas

2020

Transfusion

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Background: Hypothermic storage transforms red blood cells (RBC) from smooth biconcave discocytes into increasingly spherical spiculated echinocytes and, ultimately, fragile spherocytes (S). Individual cells undergo this transformation at different rates, producing a heterogeneous mixture of RBCs at all stages of echinocytosis in each unit of stored blood. Here we investigated how washing (known to positively affect RBC properties) changes morphology of individual RBCs at the single-cell level. Study Design and Methods: We tracked the change in shape of individual RBCs (n = 2870; drawn from six 4-to 6-week-old RBC units) that were confined in an array of microfluidic wells during washing in saline (n = 1095), 1% human serum albumin (1% HSA) solution (n = 999), and the autologous storage supernatant (control, n = 776). Results: Shape recovery proceeded through the disappearance of spicules followed by the progressive smoothening of the RBC contour, with the majority of changes occurring within the initial 10 minutes of being exposed to the washing solution. Approximately 57% of all echinocytes recovered by at least one morphologic class when washed in 1% HSA (36% for normal saline), with 3% of cells in late-stage echinocytosis restoring their discoid shape completely. Approximately one-third of all spherocytic cells were lysed in either washing solution. Cells washed in their autologous storage supernatant continued to deteriorate during washing. Conclusion: Our findings suggest that the replacement of storage supernatant with a washing solution during washing induces actual shape recovery for RBCs in all stages of echinocytosis, except for S that undergo lysis instead.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 58%

Dynamics of shape recovery by stored red blood cells during washing at the single cell level

Shevkoplyas

2020

Transfusion

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“…Of note, the number of CD235a + /AnV + microparticles in washed RBCs was higher than in standard RBCs following irradiation and storage. We have previously observed similar results, whereby the number of CD235a + /AnV + microparticles in washed RBCs was higher than in unwashed RBCs by day 14 post-wash. 21 While others have shown a reduction in red cell microparticles after washing, 22 this difference can readily be accounted for. Previous studies identified microparticles using only CD235a and size, 22 whereas we used size, CD235a, and annexin-V.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously observed similar results, whereby the number of CD235a + /AnV + microparticles in washed RBCs was higher than in unwashed RBCs by day 14 post-wash. 21 While others have shown a reduction in red cell microparticles after washing, 22 this difference can readily be accounted for. Previous studies identified microparticles using only CD235a and size, 22 whereas we used size, CD235a, and annexin-V. Furthermore, processing conditions such as the centrifugation speed, manual versus automated washing procedures, washing solutions, and post-wash storage solution influence microparticle generation.…”

Section: Discussionmentioning

confidence: 99%

X‐ and gamma‐irradiation have similar effects on the in vitro quality of stored red cell components

et al. 2021

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Background: Blood components are irradiated to inactivate lymphocytes to prevent transfusion-associated graft versus host disease. As there are little data regarding the effects of X-irradiation on red blood cell components (RBCs), the in vitro quality of stored red cells (standard, pediatric, washed, and intrauterine transfusion [IUT]) following X-or gamma-irradiation was compared. Study design and methods: RBCs were pooled, split, and processed to produce standard (<14 days and < 5 days post-collection), pediatric (<5 days post-collection), washed (<14 days post-collection), or IUT RBCs (<5 days post-collection).Standard RBCs were either X-or gamma-irradiated (n = 10 pairs). A further 10 replicates were prepared by pooling and splitting three matched RBCs (X-, gamma-, and non-irradiated). All other RBCs were either X-or gamma-irradiated (n = 20 pairs). Red cell indices, hemolysis, potassium release, metabolism, microparticles, ATP, and 2,3-DPG were measured pre-irradiation and 6 h, 1, 2, 3, 7, 10, and 14 days post-irradiation, depending on the component type. Data were analyzed using two-way repeated measures ANOVA.Results: There were no significant differences in any in vitro quality measurements, with the exception of marginally higher potassium release in washed, IUT, and RBCs <5 days old (p < .0001) following X-irradiation.Both irradiation types increased generation of microvesicles, particularly in components that were older at the time of irradiation or stored for longer post-irradiation. Conclusion: X-and gamma-irradiation have similar effects on the in vitro quality of RBCs, indicating that either technology is suitable for blood component irradiation.

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“…The storage lesion is associated with oxidation of cellular structures, [6][7][8] depletion of key metabolites such as ATP and hemoglobin (Hb) regulator 2,3-diphosphoglycerate, 9 and microvesicle formation. 10,11 Microvesicle formation is thought to be a main cause of posttransfusion complications due to their role in: (a) the pathogenesis of thrombosis, 12 inflammation, [13][14][15] and responses to pathogens; 16 (b) platelet activation; 17 (c) deformability changes that affect RBC rheology and blood flow; 18 and (d) decreased oxygen delivery due to microvesicle-entrapped Hb, 19 among others. The extent of this storage lesion is highly variable depending on factors including, but not limited to, blood processing methods, [20][21][22][23][24] storage additive solutions, [25][26][27] and donorrelated characteristics.…”

mentioning

confidence: 99%

Donor‐dependent aging of young and old red blood cell subpopulations: Metabolic and functional heterogeneity

et al. 2020

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Background: Characteristics of red blood cells (RBCs) are influenced by donor variability. This study assessed quality and metabolomic variables of RBC subpopulations of varied biologic age in red blood cell concentrates (RCCs) from male and female donors to evaluate their contribution to the storage lesion. Study Design and Methods: Red blood cell concentrates from healthy male (n = 6) and female (n = 4) donors were Percoll separated into less dense ("young", Y-RCCs) and dense ("old", O-RCCs) subpopulations, which were assessed weekly for 28 days for changes in hemolysis, mean cell volume (MCV), hemoglobin concentration (MCHC), hemoglobin autofluorescence (HGB), morphology index (MI), oxygen affinity (p50), rigidity, intracellular reactive oxygen species (ROS), calcium ([Ca 2+ ]), and mass spectrometry-based metabolomics. Results: Young RCCs having disc-to-discoid morphology showed higher MCV and MI, but lower MCHC, HGB, and rigidity than O-RCCs, having discoid-tospheroid shape. By Day 14, Y-RCCs retained lower hemolysis and rigidity and higher p50 compared to O-RCCs. Donor sex analyses indicated that females had higher MCV, HGB, ROS, and [Ca 2+ ] and lower hemolysis than male RBCs, in addition to having a decreased rate of change in hemolysis by Day 28. Metabolic profiling indicated a significant sex-related signature across all groups with increased markers of high membrane lipid remodeling and antioxidant capacity in Y-RCCs, whereas O-RCCs had increased markers of oxidative stress and decreased coping capability. Conclusion: The structural, functional, and metabolic dissimilarities of Y-RCCs and O-RCCs from female and male donors demonstrate RCC heterogeneity, where RBCs from females contribute less to the storage lesion and age slower than males.

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Platelet vesicles are potent inflammatory mediators in red blood cell products and washing reduces the inflammatory phenotype

Cited by 9 publications

References 71 publications

Dynamics of shape recovery by stored red blood cells during washing at the single cell level

Dynamics of shape recovery by stored red blood cells during washing at the single cell level

X‐ and gamma‐irradiation have similar effects on the in vitro quality of stored red cell components

Donor‐dependent aging of young and old red blood cell subpopulations: Metabolic and functional heterogeneity

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