Discocyte‐Echinocyte Reversibility in Blood Stored in CPD over a Period of 56 Days

Laczkó, J; Féo, C; Phillips, William H.

doi:10.1046/j.1537-2995.1979.19479250174.x

Cited by 40 publications

(30 citation statements)

References 17 publications

(1 reference statement)

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“…These changes include loss of metabolites (e.g. ATP), loss of RBC volume with accompanying formation of echinocytic forms and hemoglobin-containing microparticles, RBC degradation, and release of cell-free hemoglobin (hemolysis), iron, and cellular debris[12]. While potential toxic effects of each of these aspects of RBC storage have been studied (see below), little attention has been given to the potential of heme released during storage as a mediator of transfusion injury.…”

Section: Introductionmentioning

confidence: 99%

Red blood cell washing, nitrite therapy, and antiheme therapies prevent stored red blood cell toxicity after trauma–hemorrhage

Stapley

Rodriguez

et al. 2015

Free Radical Biology and Medicine

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Transfusion of stored red blood cells (RBCs) is associated with increased morbidity and mortality in trauma patients. Pro-oxidant, pro-inflammatory and nitric oxide (NO) scavenging properties of stored RBC are thought to underlie this association. In this study we determined the effects of RBC washing, nitrite and anti-heme therapy on stored RBC-dependent toxicity in the setting of trauma-induced hemorrhage. A murine (C57bl/6) model of trauma-hemorrhage and resuscitation with 1 or 3 units of RBC stored for 0–10d was used. Tested variables included whether washing RBC to remove lower MWt components that scavenge NO, NO-repletion therapy using nitrite or mitigation of free heme-toxicity by heme scavenging or preventing TLR4 activation. Stored RBC toxicity was determined by assessment of acute lung injury indices (airway edema and inflammation) and survival. Transfusion with 5d RBC increased acute lung injury indexed by BAL protein and neutrophil accumulation. Washing 5d RBC prior to transfusion did not decrease this injury, whereas nitrite therapy did. Transfusion with 10d RBC elicited a more severe injury resulting in ~90% lethality, compared to <15% with 5d RBC. Both washing and nitrite therapy significantly protected against 10d RBC-induced lethality, suggesting that washing may be protective when the injury stimulus is more severe. Finally, a spectral deconvolution assay was developed to simultaneously measure free heme and hemoglobin in stored RBC supernatants, which demonstrated significant increases of both in stored human and mouse RBC. Transfusion with free heme partially recapitulated the toxicity mediated by stored RBC. Furthermore, inhibition of TLR4 signaling, which is stimulated by heme, using TAK-242, or hemopexin-dependent sequestration of free heme significantly protected against both 5d and 10d mouse RBC-dependent toxicity. These data suggest that RBC washing, nitrite therapy and / or anti-heme and TLR4 strategies may prevent stored RBC toxicities.

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Section: Introductionmentioning

confidence: 99%

Red blood cell washing, nitrite therapy, and antiheme therapies prevent stored red blood cell toxicity after trauma–hemorrhage

Stapley

Rodriguez

et al. 2015

Free Radical Biology and Medicine

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“…For example, the reversibility of several of the metabolic and morphologic characteristics of stored blood upon ATP repletion distinguishes the stored from the senescent cell (2,12). Furthermore, events that characterize in vivo aging, such as the interactions between reticuloendothelial cells and RBCs resulting in membrane remodeling, do not occur during blood storage.…”

Section: Introductionmentioning

confidence: 99%

Transbilayer mobility and distribution of red cell phospholipids during storage.

Geldwerth¹,

Kuypers²,

Bütikofer³

et al. 1993

J. Clin. Invest.

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We studied phospholipid topology and transbilayer mobility in red cells during blood storage. The distribution of phospholipids was determined by measuring the reactivity of phosphatidylethanolamine with fluorescamine and the degradation of phospholipids by phospholipase A2 and sphingomyelinase C. Phospholipid mobility was measured by determining transbilayer movements of spin-labeled phospholipids. We were unable to detect a change in the distribution of endogenous membrane phospholipids in stored red cells even after 2-mo storage. The rate of inward movement of spin-labeled phosphatidylethanolamine and phosphatidylserine was progressively reduced, whereas that for phosphatidylcholine was increased. These changes in phospholipid translocation correlated with a fall in cellular ATP. However, following restoration of ATP, neither the rate of aminophospholipid translocation nor the transbilayer movement of phosphatidylcholine were completely corrected. Taken together, our findings demonstrate that red cell storage alters the kinetics of transbilayer mobility of phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine, the activity of the aminophospholipid translocase, but not the asymmetric distribution ofendogenous membrane phospholipids, at least at a level detectable with phospholipases.

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“…The predominance of intracellular factors is sup ported by the reversibility of these phenom ena. The echinocyte-discocyte transforma tion has been shown to be temperature-and time-dependent [14], The correlation be tween shape and ATP content of RBC has previously been studied by Sheetz and Sin ger [19], The ATP may have an indirect ef fect on shape transformation. In our study, the echinocytes appeared after 2 weeks of storage when ATP was not markedly de creased.…”

Section: Discussionmentioning

confidence: 98%

Preservation of Human Erythrocytes in the Liquid State: Biological Results with a New Medium

Herve¹,

Lamy²,

Peters³

et al. 1980

Vox Sanguinis

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Red blood cells (RBC) were collected with citrate-phosphate-dextrose (CPD) in a blood-pack optimal additive system. After concentration to 90% hematocrit they were diluted with saline-adenine-glucose medium (SAG-RBC), and stored for 35 days. In this work the RBC were stored in the presence of leukocytes. The SAG medium allows RBC conservation during 35 days at +4°C. The adenosine triphosphate (ATP) level of RBC is compatible with their survival. During the first 2 weeks, hemolysis of SAG-RBC was not greater than in CPD blood. Nevertheless, hemolysis reached 1.49% on day 35, and there was a marked increase in RBC osmotic fragility. Scanning electron-microscopic studies of 35-day RBC showed that the majority of them became echinocytes. After incubation in fresh frozen plasma, the RBC recovered satisfactory osmotic resistance and normal disc shape. The post-transfusion viability was normal with >70% recovery after 48 h. The in vivo restoration of 2,3-diphosphoglycerate (2,3-DPG) was rapid in the transfused SAG-RBC, 50% of the initial 2,3-DPG level being restored in 1 h. The in vivo studies proved that the functional quality of these RBC was compatible with their use in transfusion. The most important problem concerns the supernatant hemoglobin level of the SAG-RBC to be used for massive transfusion.

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Discocyte‐Echinocyte Reversibility in Blood Stored in CPD over a Period of 56 Days

Cited by 40 publications

References 17 publications

Red blood cell washing, nitrite therapy, and antiheme therapies prevent stored red blood cell toxicity after trauma–hemorrhage

Red blood cell washing, nitrite therapy, and antiheme therapies prevent stored red blood cell toxicity after trauma–hemorrhage

Transbilayer mobility and distribution of red cell phospholipids during storage.

Preservation of Human Erythrocytes in the Liquid State: Biological Results with a New Medium

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