Transfusion of older red blood cell units, cytokine burst and alloimmunization: a case–control study

Abstract

BackgroundExperimental data have shown that the transfusion of older red blood cell units causes alloimmunization, but the clinical applicability of this statement has never been properly assessed in non-sickle cell patients. It has been hypothesized that older units have higher numbers of cytokines, increasing the risk of alloimmunization related to antigen-presenting events. The goal of this study was to evaluate the association between the transfusion of older red blood cell units subjected to bedside leukodepletion and alloimmunization.MethodsAll patients submitted to transfusions of bedside leukodepletion red blood cell units proven to have become alloimmunized in one oncologic service between 2009 and 2013 were enrolled in this study. A control group was formed by matching patients without alloimmunization in terms of number of transfusions and medical specialty. The median age of transfused units, the percentage of transfused red blood cell units >14 days of storage in relation to fresher red cell units (≤14 days of storage) and the mean age of transfused units older than 14 days were compared between the groups.ResultsAlloimmunized and control groups were homogeneous regarding the most relevant clinical variables (age, gender, type of oncological disease) and inflammatory background (C-reactive protein and Karnofsky scale). The median age of transfused red blood cell units, the ratio of older units transfused compared to fresher units and the mean age of transfused units older than 14 days did not differ between alloimmunized and control patients (17 vs. 17; 68/32 vs. 63.2/36.8 and 21.8 ± 7.0 vs. 21.04 ± 7.9; respectively).ConclusionThe transfusion of older red blood cell units subjected to bedside leukodepletion is not a key risk factor for alloimmunization. Strategies of providing fresh red cell units aiming to avoid alloimmunization are thus not justified.

Red blood cell storage and alloimmunization: a fact or a myth?

“…Some factors known to influence RBC alloimmunization identified in murine models are in the process of being investigated in humans. Although the results obtained by Dinardo et al 11 are in agreement with other retrospective human studies 8 , 9 and strongly suggest that the transfusion of older RBC units is not a risk factor for alloimmunization, we should consider that most studies are retrospective and do not compare pre-transfusion samples to post-transfusion samples. Therefore, it is unclear as to whether the presence of an alloantibody is necessarily the result of a previous transfusion.…”

“…An important retrospective case–control study was performed of a group of alloimmunized patients and non-alloimmunized controls with solid cancer tumors that received non-phenotyped RBC transfusions when the transfusion of older RBC units was investigated as a risk factor for alloimmunization. 11 This was the first human study that evaluated the risk of alloimmunization with the transfusion of older RBCs that assured a similar inflammatory background between the study groups. The authors assessed the association between the transfusion of older RBC units (storage time of 14 days) subjected to bedside leukodepletion and alloimmunization in order to confirm previous experimental results and concluded that the transfusion of older RBC units is not a key risk factor for alloimmunization in non-SCD patients.…”

The Nlrp3 Inflammasome Does Not Regulate Alloimmunization to Transfused Red Blood Cells in Mice

“…Of note, it is not known whether the findings observed in the HOD model will translate to murine RBCs expressing other antigens, or to humans. Human studies investigating the role of RBC storage duration on alloimmunization and other adverse effects have reported varied outcomes ( Dinardo et al, 2015 , Yazer and Triulzi, 2010 , Zalpuri et al, 2013 , Desai et al, 2015 , Koch et al, 2008 , Offner et al, 2002 , Purdy et al, 1997 , Vandromme et al, 2009 , Weinberg et al, 2008 , Zallen et al, 1999 , Fergusson et al, 2012 , Lacroix et al, 2015 , Steiner et al, 2015 ) Future studies are needed in animals and humans, to determine which immune pathways are common or divergent.…”

Understanding red blood cell alloimmunization triggers

“…These studies, reviewed elsewhere, have focused primarily on mortality and outcomes such as length of intensive care unit stay; few prospective studies of RBC storage duration have included RBC alloimmunization as an outcome measure. The human studies that have investigated this issue have largely concluded that storage duration does not impact alloimmunization, [16][17][18] although at least 1 study has shown human RBCs of greater storage duration are more readily phagocytosed using an in vitro assay 19 ; another study has shown a relationship between storage age and alloimmunization in the setting of sickle cell disease. 20 Reductionist murine studies have also shown increased phagocytosis of stored compared with fresh RBCs, 21 along with increased rates/magnitudes of alloimmunization for some but not all RBC antigens.…”