Storage Time of Red Blood Cells and Mortality of Transfusion Recipients Rutger A. Middelburg ⁎, Leo M.G. van de Watering, Ernest Briët, Johanna G. van der Bom Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands Jon J. van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands abstract article info Article history: Available online 14 August 2012 Storage of red cells and the associated storage lesion have been suggested to contribute to adverse clinical outcomes. The aim of this study was to investigate whether increasing storage time of red cells is associated with mortality of recipients. From all patients who received red cell transfusions between January 2005 and May 2009, in the Leiden University Medical Center, we selected those who received only-young or only-old red cells, defined as below or above the median storage time. Mortality was compared in a Cox regression model. Subsequently, similar comparisons were made between subgroups with increasing contrast between old and young red cells. Among adult patients, after correction for potential confounders, the hazard ratio of death within 1 year after receiving red cells stored for more than 17 days compared with 17 days or less was 0.98 (95% confidence interval, 0.83-1.2). With increasing contrast, the hazard ratio decreased to 0.56 (95% confidence interval, 0.32-0.97) for red cells stored for more than 24 days compared with less than 10 days. In contrast to what has previously been suggested, we find an almost 2-fold increase in mortality rate after the transfusion of fresh red cells compared with old red cells. Results dependent on analyses chosen and previous studies may not have used optimal analyses. The tendency to demand ever-fresher blood could actually be detrimental for at least some patient groups. © 2013 Elsevier Inc. All rights reserved. STORAGE OF RED blood cells time-dependently leads to changes in cellular function, collectively referred to as the storage lesion [1,2]. As a result of this storage lesion, the overall efficacy of transfusions of older red cell has been called into question [3–6]. Furthermore, it has been suggested that the risk of some adverse effects of red cell transfusions could be increased after transfusion of older red cells [7]. Reduced efficacy and increased risk of adverse effects could together contribute to a variety of negative outcomes, which, in observational studies, have repeatedly been shown to be associated with storage time of red cells [8,9]. However, other studies have not been able to confirm these findings [10–13]. As also noted in a recent review of the evidence on the relation between red cell storage time and negative outcomes, this discrepancy could be at least partly due to differences in production methods of red cell products [14]. Some discrepancies might also be explained by the use of analyses methods not optimally suited for the data at hand, leading to biased estimates in some studies. Several large randomized studies are now underway to investigate the clinical relevance of storage time of red cells, without the potential pitfalls that many observational studies have fallen into [15–18]. There can be little doubt that these randomized trials will provide valuable information on this controversial topic, but they will take many years to complete and analyze. Many patients already receive blood essentially randomly with respect to storage time. Well- designed observational studies could therefore provide some of the same answers, as intentionally randomized studies will. Using existing transfusion databases could help provide these answers much more quickly than randomized trials could. Furthermore, if the current controversy does indeed stem from differences between red cell products, we would need randomized trials for every possible type of red cell product, or trials stratified by type of red cell product, which would consequently be prohibitively large. Observational studies into individual production methods for red cells are much easier and cheaper to perform and, if designed and analyzed properly, could each give high-quality information on the type of red cell product under investigation. These different products could then be compared by comparing the different observational studies investigating each of these products individually. We aimed to quantify the relation between recipient mortality after transfusion and storage time of red blood cells, which, after whole blood donation with or without an overnight hold at room temperature, were first buffy coat depleted, subsequently further Transfusion Medicine Reviews 27 (2013) 36–43 None of the authors report a conflict of interest relevant to the research described in this paper. This study was funded by the Leiden University Medical Center and Sanquin blood supply. The funding source had no role in study design, collection of data, analysis and interpretation of data, writing of the report, or the decision to submit. ⁎ Address reprint requests to Rutger A. Middelburg, PhD, Jon J. van Rood Center for Clinical Transfusion Research, Sanquin Research, Leiden, PO Box 23370, 3001 KJ Rotterdam, the Netherlands. E-mail address: R.A.Middelburg@lumc.nl (R.A. Middelburg). 0887-7963/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.tmrv.2012.06.002 Contents lists available at SciVerse ScienceDirect Transfusion Medicine Reviews journal homepage: www.tmreviews.com