Biochemical and structural changes in RBCs stored with different plasticizers: the role of hexanol

Draper, C.J.; Greenwalt, T. J.; Dumaswala, U.J.

doi:10.1046/j.1537-2995.2002.00138.x

Cited by 23 publications

(21 citation statements)

References 39 publications

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“…The DEHP is known to have a beneficial effect on RBCs that are stored for transfusion, reducing susceptibility to hemolysis [8,9,10,29] and minimizing the formation of both echinocytes [10] and microparticles [8,9,10,11]. Hemolysis, vesicle formation, and the shape changes associated with echinocyte formation are associated with the membrane; together with the known association of DEHP with the RBC membrane [3], this makes the DEHP-membrane interactions a specific target to study.…”

Section: Discussionmentioning

confidence: 99%

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

Melzak

Uhlig

Kirschhöfer

et al. 2018

Transfus Med Hemother

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Background: During storage of red blood cell (RBC) concentrates, the plasticizer di-2-ethylhexylphthalate (DEHP) that keeps the blood bags soft leaches out and can be taken up by the RBCs. DEHP is known to be beneficial for the RBC storage quality, but the molecular mechanisms of the action are unknown. Methods: Aqueous suspensions of DEHP were added to RBCs in buffer. The morphological effects were observed on RBCs from 5 donors. Flow cytometry with annexin A5 binding was used to measure the exposed phosphatidylserine. Results: DEHP induced the formation of stomatocytes at concentrations as low as ng/ml, provided that the cell suspension was also sufficiently dilute. Some spherocytes, which were susceptible to lysis, were also formed; after lysis, RBC ghosts were seen to continue the transition to the cup-shaped stomatocyte form. Incubation with DEHP increased the exposed phosphatidylserine, an effect that was also observed in the presence of vanadate, which inhibits the ATP-dependent translocases that maintain the membrane's lipid asymmetry. Conclusions: DEHP can have an active effect on RBC shape, instead of just preventing the storage-related shape changes. The effect appears to be mediated by increased flip-flop of lipids between the leaflets of the RBC membrane.

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Section: Discussionmentioning

confidence: 99%

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

Melzak

Uhlig

Kirschhöfer

et al. 2018

Transfus Med Hemother

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“…14 Although microvesicles are relatively abundant in stored blood, 17 where vesiculation is promoted by low pH, decreased adenosine triphosphate (ATP) levels, and the anticoagulant, they are infrequent in circulating blood 14 where vesiculation primarily occurs extravascularly in the spleen. 18 When we identified microvesicles by size and staining with antiglycophorin and anti-CD59 mAb and assessed microvesicle number in healthy nontransfused controls (n ϭ 5), we found a mean of only 6 microvesicles/L blood (data not shown).…”

Section: Transfused Rbcs Are Rich In Cd59-expressing Microvesicles Amentioning

confidence: 99%

Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria

Sloand

Mainwaring

Keyvanfar

et al. 2004

Blood

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“…None of these plasticizers are devoid of potential health hazards but DINCH shows the lowest reproductive and developmental toxicity [6], which is also a DEHP-associated risk of concern for pediatric recipients. It has been previously shown that RBCs can be stored satisfactorily in BTHC-plasticized bags [12], despite inferior protection against hemolysis and vesiculation (assessed as the cell-free, membrane-bound protein concentration during storage) compared to DEHP [13]. DINCH has recently been reported to approach DEHP in terms of protection against hemolysis [14] with the advantage that it leaches less readily from the PVC matrix [15,16].…”

Section: Introductionmentioning

confidence: 99%

Blood Bag Plasticizers Influence Red Blood Cell Vesiculation Rate without Altering the Lipid Composition of the Vesicles

Bicalho

Serrano

Pereira

et al. 2015

Transfus Med Hemother

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Background: Polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate (DEHP) is commonly used for blood collection and storage. DEHP has protective effects on RBC membranes, but is also a toxin. Methods: A paired study was conducted to investigate the influence of DEHP and two alternative plasticizers, 1,2-cyclohexane-dicarboxylic acid diisononyl ester (DINCH) and n-butyryl-tri-n-hexyl citrate (BTHC), on the preservation of RBCs stored for 42 days in PVC pediatric bags. The RBC membrane was evaluated for supernatant hemoglobin (Hb), release of extracellular microvesicles (EVs), osmotic fragility, deformability, and lipid composition. Results: In BTHC-plasticized bags, the supernatant Hb increase during storage was 2 times greater than in DINCH- and DEHP-plasticized bags. By day 21, EV concentrations had doubled from day-5 levels in DINCH- and DEHP-, and trebled in BTHC-plasticized bags. RBC mean cell volumes were greater in BTHC- than in DINCH- or DEHP-plasticized bags (p < 0.001). Osmotic fragility differed significantly among plasticizers (p < 0.01). After day 21, RBC deformability decreased in all, but to a greater extent in the bags with BTHC. Phospholipid composition of RBCs and EVs was not different among plasticizers. Conclusion: Membrane stabilization capacity differed among the plasticizers. RBC in BTHC bags stored more poorly, while DEHP and DINCH bags offered better protection against vesiculation, osmotic stress, and Hb loss.

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Biochemical and structural changes in RBCs stored with different plasticizers: the role of hexanol

Cited by 23 publications

References 39 publications

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

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

Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria

Blood Bag Plasticizers Influence Red Blood Cell Vesiculation Rate without Altering the Lipid Composition of the Vesicles

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