The Blood Bag Plasticizer Di-2-Ethylhexylphthalate Causes Red Blood Cells to Form Stomatocytes, Possibly by Inducing Lipid Flip-Flop

Melzak, Kathryn A.; Uhlig, Stefanie; Kirschhöfer, Frank; Brenner‐Weiß, Gerald

doi:10.1159/000490502

Cited by 18 publications

(15 citation statements)

References 44 publications

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“…Sicińska (2018) demonstrated that DBP and BBP induce haemolysis in human erythrocytes at concentrations of 10 and 5 lg/mL, respectively and eryptosis at concentrations of 1 lg/mL DBP and 2.5 lg/mL BBP. On the other hand DEHP induce the formation of stomatocytes in red blood cells (RBCs) at concentrations as low as ng/mL (Melzak et al 2018). These agree with the results obtained in the present work, given that at concentrations of 100 lg/mL DBP, BBP and DEHP had the highest toxicity (Fig.…”

Section: Discussionsupporting

confidence: 92%

Phthalates affect the in vitro expansion of human hematopoietic stem cell

et al. 2019

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Phthalates are esters of phthalic acid used industrially as plastic additives, however, these are not covalently bound to the polymer matrix and therefore can be released to the environment. The aim of this study was to evaluate the effect of four phthalates: dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), diethyl phthalate (DEP) and diethylhexyl phthalate (DEHP) on the in vitro expansion of human hematopoietic cells from umbilical cord blood. For this, 0.5 9 10 6 cells/mL were exposure to concentrations ranging from 0.1 to 100 lg/mL and the total cell expansion was determined after 14 days of culture in IMDM-cytokines medium. The control cultures attained 1.31 ± 0.21 9 10 6 cell/mL, whereas the cultures exposed to DBP, BBP and DEHP showed a reduction from 23 to 81%, 17 to 69% and 15 to 93.5%, respectively. DEP did not affect the total cell expansion. The most significant decrease on total cell expansion was observed at 0.1 lg/mL DBP, 100 lg/mL BBP and 10 lg/mL DEHP (p \ 0.05). Additionally, the effect of these compounds on the expansion of hematopoietic progenitors was analyzed by clonogenic assays as colony forming units (CFU). The CFU decreased considerably compared with respect to the control cultures. The reduction was 74.6 and 99.1% at 10 and 100 lg/mL DBP respectively, whereas 100 lg/mL BBP and 100 lg/mL DEHP reduced the CFU expansion in 97.1% and 81%, respectively. Cultures exposed to DEP did not show significant differences. The results demonstrate the toxicity of DBP, BBP and DEHP on the human hematopoietic stem cells.

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Section: Discussionsupporting

confidence: 92%

Phthalates affect the in vitro expansion of human hematopoietic stem cell

et al. 2019

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“…The release of MPs continues throughout their lifespan. Therefore, their number gradually increases with the storage time in the erythrocyte concentrate (Said et al, 2018;Melzak et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Levels of red blood cells derived microparticles in stored erythrocyte concentrate

Rana¹,

Arfat²,

Naseem³

et al. 2020

Afr. J. Pharm. Pharmacol.

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There is increasing evidence of the clinical importance of microparticles (MPs) and their role in blood transfusion-related side effects and the transmission of pathogens. The study aims to examine the red blood cell-derived MPs in blood bags during storage under standardized blood bank conditions. The samples were tested at various times to demonstrate the presence of RBC-derived MPs by flow cytometry. The quantitative assay was carried out in stored erythrocyte concentrate on days 0, 25 and 35 and their number from day 0 to 25 and 35 and the number of day 25 to day 35 were compared. The MPs were counted after being concentrated in a supernatant (labeled with the respective antibodies CD47, CD235a and Annexin V) obtained by a specific centrifugation procedure. The analysis showed that the number of Annexin V positive MPs increased between day 0 and day 35 (~ 0.001) and CD47 expression on MPs at day 25 and day 35 decreased compared to day 0 (~ 0.001). In addition, CD235a expression had shown minimal insignificant changes with an upward trend (> 0.05) during the storage period. It is concluded that monitoring the release of MPs from RBC units during storage is a sensitive approach to identifying MPs for transfusion drugs and, more broadly, for cell-based therapies.

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“…The RBCs were stored in the transfusion bags used for collection until the day of the morphology measurements. The RBCs were observed after rinsing in phosphate-buffered saline (from tablets, VWR) on an adhesive polymer layer as described previously [13, 18] using a phase-contrast microscope (Zeiss Axiovert A1 with a 40× objective, NA = 0.55) and a Zeiss AxioCam ICc1 camera. Details of slide preparation are described in the online supplementary material (for all online suppl.…”

Section: Methodsmentioning

confidence: 99%

“…1), thus leading to the formation of stomatocytes. Stomatogenic agents include decreased pH [7, 9], agents that insert selectively into the inner leaflet [3], albumin, which extracts lipids from the outer leaflet [10-12], and the plasticiser that leaches out of standard transfusion bags and which may promote scrambling of lipids from the two membrane leaflets [13].…”

Section: Introductionmentioning

confidence: 99%

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

Melzak

Spouge

Boecker

et al. 2020

Transfus Med Hemother

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Background: Red blood cells (RBCs) stored for transfusions can lyse over the course of the storage period. The lysis is traditionally assumed to occur via the formation of spiculated echinocyte forms, so that cells that appear smoother are assumed to have better storage quality. We investigate this hypothesis by comparing the morphological distribution to the hemolysis for samples from different donors. Methods: Red cell concentrates were obtained from a regional blood bank quality control laboratory. Out of 636 units processed by the laboratory, we obtained 26 high hemolysis units and 24 low hemolysis units for assessment of RBC morphology. The association between the morphology and the hemolysis was tested with the Wilcoxon-Mann-Whitney U test. Results: Samples with high stomatocyte counts (p = 0.0012) were associated with increased hemolysis, implying that cells can lyse via the formation of stomatocytes. Conclusion: RBCs can lyse without significant echinocyte formation. Lower degrees of spiculation are not a good indicator of low hemolysis when RBCs from different donors are compared.

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The Blood Bag Plasticizer Di-2-Ethylhexylphthalate Causes Red Blood Cells to Form Stomatocytes, Possibly by Inducing Lipid Flip-Flop

Cited by 18 publications

References 44 publications

Phthalates affect the in vitro expansion of human hematopoietic stem cell

Phthalates affect the in vitro expansion of human hematopoietic stem cell

Levels of red blood cells derived microparticles in stored erythrocyte concentrate

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

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