Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial

Cook, Richard J.; Heddle, Nancy M.; Lee, Ker‐Ai; Arnold, Donald M.; Crowther, Mark; Devereaux, P.J.; Ellis, Martin; Figueroa, Priscilla; Kurz, Andrea; Roxby, David; Sessler, Daniel I.; Sharon, Yehudit; Sobieraj‐Teague, Magdalena; Warkentin, Theodore E.; Webert, Kathryn E.; Barty, Rebecca; Liu, Yang; Eikelboom, John W.

doi:10.1016/s2352-3026(17)30169-2

Cited by 33 publications

(35 citation statements)

References 15 publications

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“…22 The association between PRBC >30 days old and mortality differed from secondary analyses of the Informing Fresh versus Old Red Cell Management (INFORM) study. 23 In the secondary analyses, the use of maximum PRBC age to define stored PRBCs may have overestimated the aggregate PRBC age transfused. 24 Patients transfused with predominantly fresh PRBC units, but with the addition of one PRBC unit >35 days old could inflate the number of “survivors” in the stored PRBC group.…”

Section: Discussionmentioning

confidence: 99%

Transfusion of packed red blood cells at the end of shelf life is associated with increased risk of mortality – a pooled patient data analysis of 16 observational trials

David

Middelburg

et al. 2018

Haematologica

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Observational studies address packed red blood cell effects at the end of shelf life and have larger sample sizes compared to randomized control trials. Meta-analyses combining data from observational studies have been complicated by differences in aggregate transfused packed red blood cell age and outcome reporting. This study abrogated these issues by taking a pooled patient data approach. Observational studies reporting packed red blood cell age and clinical outcomes were identified and patient-level data sets were sought from investigators. Odds ratios and 95% confidence intervals for binary outcomes were calculated for each study, with mean packed red blood cell age or maximum packed red blood cell age acting as independent variables. The relationship between mean packed red blood cell age and hospital length of stay for each paper was analyzed using zero-inflated Poisson regression. Random effects models combined paper-level effect estimates. Extremes analyses were completed by comparing patients transfused with mean packed red blood cell aged less than ten days to those transfused with mean packed red blood cell aged at least 30 days. sixteen datasets were available for pooled patient data analysis. Mean packed red blood cell age of at least 30 days was associated with an increased risk of in-hospital mortality compared to mean packed red blood cell of less than ten days (odds ratio: 3.25, 95% confidence interval: 1.27–8.29). Packed red blood cell age was not correlated to increased risks of nosocomial infection or prolonged length of hospital stay.

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Section: Discussionmentioning

confidence: 99%

Transfusion of packed red blood cells at the end of shelf life is associated with increased risk of mortality – a pooled patient data analysis of 16 observational trials

David

Middelburg

et al. 2018

Haematologica

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“…39,40 A secondary analysis of the INFORM clinical trial data which had enough data to evaluate the effect of RBCs stored >35 days did not detect differences in in-hospital mortality between patients transfused with at least one unit older than 35 days, and patients transfused with units less than 8 days; however, other clinical outcomes were not evaluated in this trial. 41 The apparent disconnect between studies could possibly in part be explained by the role that biological variability (both of donors and recipients) and processing strategies play on the development of the storage lesion and clinical outcomes. 42 …”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

et al. 2018

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Background Biological and technical variability has been increasingly appreciated as a key factor impacting red blood cell (RBC) storability and, potentially, transfusion outcomes. Here we performed metabolomics analyses to investigate the impact of factors other than storage duration on the metabolic phenotypes of stored RBC in a multi-center study. Study design and Methods Within the framework of the REDS-III RBC-Omics study, 13,403 donors were enrolled from four blood centers across the United States and tested for the propensity of their RBCs to hemolyze after 42 days of storage. Extreme hemolyzers were recalled and donated a second unit of blood. Units were stored for 10, 23 and 42 days prior to sample acquisition for metabolomics analyses. Results Unsupervised analyses of metabolomics data from 599 selected samples revealed a strong impact (14.2% of variance) of storage duration on metabolic phenotypes of RBCs. The blood center collecting and processing the units explained an additional 12.2% of the total variance, a difference primarily attributable to the storage additive (AS-1 vs AS-3) used in the different hubs. Samples stored in mannitol-free/citrate-loaded AS-3 were characterized by elevated levels of high-energy compounds, improved glycolysis and glutathione homeostasis. Increased methionine metabolism and activation of the trans-sulfuration pathway was noted in samples processed in the center using AS-1. Conclusion Blood processing impacts the metabolic heterogeneity of stored RBCs from the largest multi-center metabolomics study in transfusion medicine to date. Studies are needed to understand if these metabolic differences influenced by processing/storage strategies impact the effectiveness of transfusions clinically.

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“…Nonetheless, rigorous patient selection, uniformly applied blood preparation, and transfusion practices strictly based on institutional protocols along with standardized anesthetic and surgical management helped minimize the risk for bias. Second, RBCs can be stored for as long as 35 days in South Korea; thus the impact of RBCs stored for more than 35 days were not evaluated, even though previous studies reported conflicting results regarding this issue . However, our study had advantages as well.…”

Section: Discussionmentioning

confidence: 97%

Longer storage of red blood cells does not affect mortality in transfused liver transplant recipients

Kwon¹,

Han²,

Cho

et al. 2018

Transfusion

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BACKGROUND The characteristics of red blood cell (RBC) products change after 2 weeks of cold storage. It is unclear whether older RBCs affect mortality after liver transplantation. This retrospective cohort study aimed to evaluate the association between the age of transfused RBCs and death after living donor liver transplantation (LDLT). STUDY DESIGN AND METHODS Of 200 recipients who underwent LDLT, 118 who received RBCs with a mean storage duration of less than 10 days (shorter storage group) were compared with 82 with an RBC mean storage duration of more than 14 days (longer storage group). Key exclusion criteria were transfusion of very fresh RBCs stored for less than 4 days and transfusion of old RBCs in recipients of the shorter storage group. The primary outcome was posttransplant overall death. Survival analysis was performed using the Cox model. RESULTS Mean RBC storage duration was 7 days in the shorter storage group and 17 days in the longer storage group. Death probability at 1, 2, and 5 years posttransplant was 5.1%, 7.6%, and 13.6% in the shorter storage group, respectively, and 6.1%, 8.5%, and 13.5% in the longer storage group. Death risk was comparable between the two groups in univariable (hazard ratio [HR] 1.00, 95% confidence interval [CI], 0.47‐2.16, p = 0.991) and multivariable (HR 1.07, 95% CI, 0.46‐2.50, p = 0.882) analyses. Graft failure risk was also comparable (HR 1.04, 95% CI, 0.50‐2.18, p = 0.916). Hepatocellular carcinoma recurrence probability at 1, 2, and 5 years was 10.8%, 15.4%, and 23.1%, respectively, in the shorter storage group and 11.4%, 15.9%, and 20.7% in the longer storage group (HR 0.84, 95% CI, 0.37‐1.89, p = 0.670). No significant differences were observed regarding graft regeneration/function, vascular/biliary complications, acute kidney injury, surgical site infection, or rejection (p > 0.05). CONCLUSIONS No evidence was found that transfusion of old RBCs contributes to death after LDLT.

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Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial

Cited by 33 publications

References 15 publications

Transfusion of packed red blood cells at the end of shelf life is associated with increased risk of mortality – a pooled patient data analysis of 16 observational trials

Transfusion of packed red blood cells at the end of shelf life is associated with increased risk of mortality – a pooled patient data analysis of 16 observational trials

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

Longer storage of red blood cells does not affect mortality in transfused liver transplant recipients

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