Association between duration of storage of transfused red blood cells and morbidity and mortality in adult patients: myth or reality?

Lelubre, Christophe; Piagnerelli, Michaël; Vincent, Jean‐Louis

doi:10.1111/j.1537-2995.2009.02211.x

Cited by 158 publications

(163 citation statements)

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“…This is especially true for certain categories of recipients, such as traumatized, post-operative and critically ill patients. 1 Despite accumulating retrospective evidence of reduced blood viability after the first 2 weeks of storage, 2 definitive results from prospective, randomized, double-blind clinical trials are still lacking 3,4 or inconclusive. These problems are mainly due to the intrinsic statistical limitations of the experimental models 4 or the lack of common methods and shared standards between laboratories.…”

Section: Introductionmentioning

confidence: 99%

Time-course investigation of SAGM-stored leukocyte-filtered red bood cell concentrates: from metabolism to proteomics

D’Alessandro¹,

D’Amici²,

Vaglio³

et al. 2011

Haematologica

184

205

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The online version of this article has a Supplementary Appendix. BackgroundResults from recent, highly debated, retrospective studies raised concerns and prompted considerations about further testing the quality of long stored red blood cells from a biochemical standpoint. Design and MethodsWe performed an integrated mass spectrometry-based metabolomics and proteomics timecourse investigation on SAGM-stored red blood cells. In parallel, structural changes during storage were monitored through scanning electron microscopy. ResultsWe detected increased levels of glycolytic metabolites over the first 2 weeks of storage. From day 14 onwards, we observed a significant consumption of all metabolic species, and diversion towards the oxidative phase of the pentose phosphate pathway. These phenomena coincided with the accumulation of reactive oxygen species and markers of oxidation (protein carbonylation and malondialdehyde accumulation) up to day 28. Proteomics evidenced changes at the membrane protein level from day 14 onwards. Changes included fragmentation of membrane structural proteins (spectrin, band 3, band 4.1), membrane accumulation of hemoglobin, antioxidant enzymes (peroxiredoxin-2) and chaperones. While the integrity of red blood cells did not show major deviations at day 14, at day 21 scanning electron microscope images revealed that 50% of the erythrocytes had severely altered shape. We could correlate the scanning electron microscopy observations with the onset of vesiculation, through a proteomics snapshot of the difference in the membrane proteome at day 0 and day 35. We detected proteins involved in vesicle formation and docking to the membrane, such as SNAP alpha. ConclusionsBiochemical and structural parameters did not show significant alterations in the first 2 weeks of storage, but then declined constantly from day 14 onwards. We highlighted several parallelisms between red blood cells stored for a long time and the red blood cells of patients with hereditary spherocytosis.Key words: red blood cell, storage, mass spectrometry, proteomics, metabolomics. Haematologica 2012;97(1):107-115. doi:10.3324/haematol.2011 Citation: D'Alessandro A, D'Amici GM, Vaglio S, and Zolla L. Time-course investigation of SAGM-stored leukocyte-filtered red blood cell concentrates: from metabolism to proteomics.

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Section: Introductionmentioning

confidence: 99%

Time-course investigation of SAGM-stored leukocyte-filtered red bood cell concentrates: from metabolism to proteomics

D’Alessandro¹,

D’Amici²,

Vaglio³

et al. 2011

Haematologica

184

205

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“…In noncardiac patients, such as cases of elective colorectal cancer surgery, two studies 30,31 with different design investigated the effects of RBC storage on postoperative infections generating conflicting results. 5 In the first study, infections occurred more frequently in patients receiving old blood (stored for more than 21 days) when compared to fresh blood (stored for <21 days; 46% vs. 32%). 30 Nevertheless, the same authors showed in a second study that infection rates were similar in patients transfused with old blood (stored > 21 days) and fresh blood (stored for < 21 days; 34% vs. 29%).…”

mentioning

confidence: 99%

“…3 Although the biochemical effects of storage on RBCs are well documented, the clinical consequences of receiving RBCs of longer storage duration are currently a matter of debate. 5 Three recent randomized clinical trials did not find significant differences between fresh and old blood in patients undergoing cardiac surgery 6 or admitted to the intensive care unit (ICU) 7 and in hospitalized patients. 8 Immunosuppression induced by surgery and anesthesia may be aggravated by transfusion.…”

mentioning

confidence: 99%

“…4 The mechanisms underlying the development of transfusion-associated immunomodulation have not yet been completely elucidated; however, studies in vivo and in vitro suggested that the storage time of RBCs may play a role in inducing immunosuppression. 5 RBCs undergo morphologic and functional changes during prolonged storage (so-called "storage lesions"), including imbalance of the cell membrane expression of CD47 and phosphatidylserine, which can contribute to activate the immune system. 3 Moreover, during storage, cytokines and other substances (e.g., histamine, immunologically active phospholipids, soluble CD40 ligand) with inflammatory and immunomodulatory properties accumulate in the supernatant and trigger the activation of immune cells.…”

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confidence: 99%

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The effects of storage of red blood cells on the development of postoperative infections after noncardiac surgery

et al. 2017

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BACKGROUND: Prolonged storage of red blood cells (RBCs) is a potential risk factor for postoperative infections. The objective of this study was to examine the effect of age of RBCs transfused on development of postoperative infection. STUDY DESIGN AND METHODS: In thisprospective, double-blind randomized trial, 199 patients undergoing elective noncardiac surgery and requiring RBC transfusion were assigned to receive nonleukoreduced RBCs stored for not more than 14 days ("fresh blood" group, n 5 101) or for more than 14 days ("old blood" group, n 5 98). The primary outcome was occurrence of infection within 28 days after surgery; secondary outcomes were postoperative acute kidney injury (AKI), in-hospital and 90-day mortality, admission to intensive care unit, and hospital length of stay (LOS). As older blood was not always available, an "as-treated" (AT) analysis was also performed according to actual age of the RBCs transfused. RESULTS:The median [interquartile range] storage time of and 15 [11][12][13][14][15][16][17][18][19][20] days in fresh blood and in old blood groups, respectively. The occurrence of postoperative infection did not differ between groups (fresh blood 22% vs. old blood 25%; relative risk [RR], 1.17; confidence interval [CI], 0.71-1.93), although wound infections occurred more frequently in old blood (15% vs. 5%; RR, 3.09; CI,). Patients receiving older units had a higher rate of AKI (24% vs. 6%; p < 0.001) and, according to AT analysis, longer LOS (mean difference, 3.6 days; CI, 0.6-7.5).CONCLUSION: Prolonged RBC storage time did not increase the risk of postoperative infection. However, old blood transfusion increased wound infections rate and incidence of AKI. Immunosuppression induced by surgery and anesthesia may be aggravated by transfusion. 9 Most studies in trauma and cardiac surgery reported that prolonged RBC storage was a risk factor for postoperative infections after cardiac surgery, 10-12 but the same association was not found in liver transplantation 13 or orthopedic surgery. 14 A recent systematic review 15 that analyzed four trials which investigated the nosocomial infections, showed no benefits in receiving fresh RBCs. However, the authors reported that the results are difficult to interpret because the studies involved different populations and there were considerable differences in the length of storage of fresh and old blood and in study methods. 15To our knowledge, the association of age of RBCs with infections in noncardiac surgery population has not been investigated by double-blind randomized studies. Accordingly, the aim of this study was to investigate the relationship between RBC storage time and postoperative infection after elective noncardiac surgery. In addition, we evaluated the effects of the age of RBCs on other outcomes such as postoperative acute kidney injury (AKI), hospital length of stay (LOS), and 90-day mortality. MATERIALS AND METHODS Study populationThis prospective, randomized, controlled, double-blind clinical trial was conducted between August 2...

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“…[16][17][18] To our knowledge, no systematic review currently exists that exclusively examines the impact of the age of transfused RBCs on mortality in the trauma patient population, although other patient populations have been investigated. [19][20][21][22][23][24] The objective of this review was to assess the available evidence for the impact of the age of stored RBCs given as transfusions in the trauma population on patient mortality.…”

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confidence: 99%

Impact of the age of stored blood on trauma patient mortality: a systematic review

et al. 2015

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Background:The impact of the age of stored red blood cells on mortality in patients sustaining traumatic injuries requiring transfusion of blood products is unknown. The objective of this systematic review was to identify and describe the available literature on the use of older versus newer blood in trauma patient populations. Methods:We searched PubMed, Embase, Lilac and the Cochrane Database for published studies comparing the transfusion of newer versus older red blood cells in adult patients sustaining traumatic injuries. Studies included for review reported on trauma patients receiving transfusions of packed red blood cells, identified the age of stored blood that was transfused and reported patient mortality as an end point. We extracted data using a standardized form and assessed study quality using the Newcastle-Ottawa Scale.Results: Seven studies were identified (6780 patients) from 3936 initial search results. Four studies reported that transfusion of older blood was independently associated with increased mortality in trauma patients, while 3 studies did not observe any increase in patient mortality with the use of older versus newer blood. Three studies associated the transfusion of older blood with adverse patient outcomes, including longer stay in the intensive care unit, complicated sepsis, pneumonia and renal dys function. Studies varied considerably in design, volumes of blood transfused and def initions applied for old and new blood. Conclusion:The impact of the age of stored packed red blood cells on mortality in trauma patients is inconclusive. Future investigations are warranted.Contexte : On ne connaît pas l'incidence de la durée de stockage des globules rouges sur la mortalité des patients atteints de lésions traumatiques qui ont besoin de transfu sions de produits sanguins. L'objectif de cette revue systématique était de trouver et d'analyser la documentation scientifique qui compare les transfusions de sang chez les patients adultes victimes de trauma en fonction de la durée de stockage du sang.Méthodes : Nous avons effectué des recherches sur PubMed, Embase et Lilac et dans la Cochrane Database of Systematic Reviews. Les études retenues portaient sur des transfusions de concentré de globules rouges chez les patients atteints de lésions traumatiques, tenaient compte de la durée de stockage du sang transfusé et faisaient état des décès de patients. Nous avons extrait les données à l'aide d'un formulaire nor malisé et évalué la qualité des études selon l'échelle Newcastle-Ottawa.Résultats : Nous avons sélectionné 7 études (totalisant 6780 patients) parmi les 3936 ré sultats de la recherche initiale. D'un côté, 4 études rapportaient que la transfu sion de sang dont la durée de stockage était longue était indépendamment associée à l'augmentation de la mortalité chez les patients atteints de lésions traumatiques; de l'autre, 3 études ne faisaient état d'aucune augmentation de la mortalité en fonction de la durée de stockage du sang transfusé. Trois études associaient la transfusion de sang s...

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Association between duration of storage of transfused red blood cells and morbidity and mortality in adult patients: myth or reality?

Abstract: From the currently available published data, it is difficult to determine whether there is a relationship between the age of transfused RBCs and outcome in adult patients, except possibly in trauma patients receiving massive transfusion.

Cited by 158 publications

References 45 publications

Time-course investigation of SAGM-stored leukocyte-filtered red bood cell concentrates: from metabolism to proteomics

Time-course investigation of SAGM-stored leukocyte-filtered red bood cell concentrates: from metabolism to proteomics

The effects of storage of red blood cells on the development of postoperative infections after noncardiac surgery

Impact of the age of stored blood on trauma patient mortality: a systematic review

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