Plasma from Aged Stored Red Blood Cells Delays Neutrophil Apoptosis and Primes for Cytotoxicity: Abrogation by Poststorage Washing but Not Prestorage Leukoreduction

Biffl, Walter L.; Moore, Ernest E.; Offner, Patrick J.; Ciesla, David J.; Gonzalez, Ricardo J.; Silliman, Christopher C.

doi:10.1097/00005373-200103000-00005

Cited by 121 publications

(101 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Direct (15). In addition, in vitro allogeneic PRBC transfusion appears to have the potential to promote polymorphonuclear cell-mediated cytotoxicity and to suppress neutrophil locomotion (16) and apoptosis (17). Our findings of significant increases in proinflammatory cytokines after transfusion are in keeping with both in vitro evidence for induction of pro-and anti-inflammatory cytokines following PRBC exposure (18,19) and adult in vivo data (20).…”

Section: Discussionsupporting

confidence: 79%

See 1 more Smart Citation

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

et al. 2012

View full text Add to dashboard Cite

Background: Transfusion of packed red blood cells (PRBcs) saves lives in the neonatal critical care setting and is one of the most common interventions in the preterm infant. The number and volume of PRBc transfusions are associated with several major neonatal morbidities, although a direct causal link between transfusion and major neonatal morbidity is still to be proven. Transfusion-related immunomodulation (TRIM) may underlie these adverse outcomes, yet it has received little attention in the high-risk preterm infant. Methods: One transfusion event was studied in infants ≤28 wk gestation between 2 and 6 wk postnatal age (n = 28). Plasma inflammatory cytokines and markers of endothelial activation were measured in the infants before and 2-4 h after transfusion, as well as in the donor pack. results: Median (range) age at transfusion was 18 (14-39) days with the pretransfusion hemoglobin level at 9.8 (7.4-10.2) g/dl. Interleukin (IL)-1β (P = 0.01), IL-8 (P = <0.001), tumor necrosis factor-α (P = 0.008), and monocyte chemoattractant protein (P = 0.01) were increased after transfusion. a similar elevation in markers of endothelial activation was seen after transfusion with increased plasma macrophage inhibitory factor (P = 0.005) and soluble intracellular adhesion molecule-1 (P = <0.001). conclusion: Production of inflammatory cytokines and immunoactivation of the endothelium observed after the transfusion of PRBcs in the preterm infant may be a manifestation of TRIM. The implications of this emerging phenomenon within the preterm neonatal population warrant further investigation. t ransfusion of blood products is not benign. In adults, transfusion is an independent predictor of death and is associated with an increased incidence of multiorgan system failure, length of hospital stay, infection risk, and modulation of the immune system (1,2). Although the mechanisms underlying these associations are yet to be comprehensively characterized, a two-hit model of posttransfusion injury has been proposed (3). In the clinical setting of an underlying inflammatory state priming the recipient's immune system, transfusion of packed red blood cells (PRBCs) may trigger immune cell activation and related immunomodulation, resulting in frank inflammation (4). This transfusion-related immunomodulation (TRIM), encompassing not only adverse proinflammatory and immunosuppressive responses but also the whole spectrum of posttransfusion effects on organs and tissues, has been proposed to underlie much of the increased transfusionassociated morbidity and mortality seen in adults (4).In the neonatal population, there is an increasing awareness of the excess morbidity and mortality associated with PRBC transfusions (5,6). PRBC transfusions have been implicated in the development of problems not encountered in the adult population, including chronic lung disease (7), retinopathy of prematurity (8), and necrotizing enterocolitis (9,10), with the incidence and severity of these conditions correlating with the number and volume of PRBC tran...

show abstract

Section: Discussionsupporting

confidence: 79%

“…In vitro, leukodepletion attenuates the IL-1β response induced in peripheral blood mononuclear cells following exposure to red blood cell supernatant but only partially mitigates the TNF-α and IL-6 responses (35). Leukodepletion has also been shown to have no effect on the PRBC transfusion-mediated priming of neutrophil cytotoxicity (17).…”

Section: Discussionmentioning

confidence: 99%

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

et al. 2012

View full text Add to dashboard Cite

show abstract

“…It has been postulated that washing removes debris, nonviable cells and unspecified metabolic breakdown products, thereby reducing possible sources of toxicity by removing supernatant hemoglobin, leukocytes and plasma. [9][10][11] Also, when older units of blood are used in massive transfusions, saline washing has been employed in an effort to reduce the risk of hyperkalemia. This latter rationale has been challenged, particularly when applied to less-than-massive volumes of blood transfused, because when small volumes are transfused, the major consideration for the patient is the total amount of K þ transfused and the transfusion rate.…”

Section: Discussionmentioning

confidence: 99%

Increased hemolysis from saline pre-washing RBCs or centrifugal pumps in neonatal ECMO

et al. 2007

View full text Add to dashboard Cite

Objectives: Hemolysis is a significant complication of extracorporeal membrane oxygenation (ECMO), with a reported incidence of 12.2%. The aims of this study were (1) to investigate hemolysis caused by saline-washed versus unwashed RBCs, (2) to determine in vitro the effects of saline washing on erythrocyte hemolytic markers and (3) to investigate hemolysis by centrifugal versus roller pumps.Study design: (1) To evaluate the effect of pre-transfusion saline-washing versus non-washing, the peak plasma-free hemoglobin (FHb) and total bilirubin in the first 3 days versus the next 4 days of ECMO were compared (2) Pre-and postsaline-washed RBCs were analyzed for K þ , hemoglobin, mean corpuscular volume, FHb and hemolysis at baseline and after 4 h of storage at 41C. (3) Over 10 000 neonatal ECMO cases were retrospectively reviewed to study the effect of pump type on hemolysis.Results: (1) The washed blood group had significantly more hemolysis within the first 3 days of ECMO. (2) Immediately after saline washing, the K þ and Hb concentrations were significantly decreased compared with unwashed blood, and these differences were maintained after 4 h. The osmotic fragility of washed RBCs after 4 h of storage at 41C was significantly higher than at baseline. (3) Hemolysis was reported more often in the centrifugal than in the roller pump group.Conclusions: (1) Using unwashed RBCs decreased hemolysis within the first 3 days of ECMO. (2) Saline washing, while decreasing the concentration of K þ in the plasma, significantly increases RBC membrane osmotic fragility. (3) Hemolysis is linked to the use of centrifugal pumps.

show abstract

“…Washing has been shown to improve the in vitro characteristics of stored RBCs. [4][5][6][7][8][9][10][14][15][16][17] Earlier generations of cells washers were labor intensive and considered "open systems," which limited the shelf life of washed cells to 24 hours. Current microprocessor-driven, closed-system cell-washers can be programmed to provide extensive cell washing and an approved shelf life of 14 days.…”

Section: Introductionmentioning

confidence: 99%

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

Cortés‐Puch

Wang

Sun

et al. 2014

Blood

107

View full text Add to dashboard Cite

• Washing older blood before transfusion reduces plasma iron, improving outcomes from established infection in canines.• In contrast, washing fresh blood before transfusion increases in vivo plasma CFH release, worsening outcomes.In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n 5 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7-or 42-dayold washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes. (Blood. 2014;123(9):1403-1411 IntroductionTransfusion of older stored canine universal donor blood in a canine model of experimental Staphylococcus aureus pneumonia results in markedly increased lung injury and mortality rates.1 Transfusion with older blood is also associated with increased levels of cell-free hemoglobin (CFH), transferrin bound iron (TBI), non-TBI (NTBI) and plasma labile iron (PLI). NTBI represents iron excess bound to proteins that do not normally handle circulating iron, and PLI is the toxic iron moiety in plasma. Whereas increased nitric oxide scavenging by CFH causing vasoconstriction and vascular injury and increased available iron promoting bacterial growth represent 2 candidate mechanisms of injury, multiple other biological changes have been documented with increasing blood storage interval.2,3 Some of these changes involve the release into the plasma of biologically active proteins, microvesicles, potassium, acid, and plasticizer, all of which can be reduced by means of standard red cell (RBC) washing procedures. [4][5][6][7][8][9][10] The clinical effect(s) of washing on the RBC storage lesion has not been studied.RBC washing has long been performed to reduce potassium levels in stored blood transfused to neonates, debris from RBCs recovered during surgery, cryoprotectant glycerol from cryopreserved RBCs, and plasma proteins from blood intended for patients who have been sensitized to those proteins.11-13 Automated cell washers cap...

show abstract

Plasma from Aged Stored Red Blood Cells Delays Neutrophil Apoptosis and Primes for Cytotoxicity: Abrogation by Poststorage Washing but Not Prestorage Leukoreduction

Cited by 121 publications

References 39 publications

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Increased hemolysis from saline pre-washing RBCs or centrifugal pumps in neonatal ECMO

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

Contact Info

Product

Resources

About