Prolonged Storage Of Red Cells Research Articles

Irradiation and prolonged storage of red cells are associated with increased adverse events.

Red blood cell (RBC) transfusion is associated with the most transfusion-related adverse events (AE). Recent clinical studies showed no significant difference in transfusion-associated mortality between fresh and older RBCs. However, the impact of storage duration as well as irradiation on nonfatal yet much more common complications has not been fully investigated. In this retrospective study of RBC transfusion-associated AEs, a total of 188,562 units of leucocyte-reduced RBCs were transfused in approximately 5·5 years. After excluding washed, deglycerolized, autologous or directed RBCs and RBCs transfused during a massive transfusion protocol, 149,052 units were analysed. Attributes of RBCs including storage time, collection method, CMV serological status and gamma irradiation, as well as the recipient's gender, were analysed. A total of 358 RBC transfusion AEs were categorized into allergic and non-allergic reactions and analysed. Univariate and multivariate logistic analyses showed that irradiated RBCs were associated with a significantly increased frequency of non-allergic reactions (OR (95% CI): 1·89 (1·52, 2·35); P < 0·001). There was a significant association between the frequency of non-allergic reactions and the storage time of irradiated RBCs (OR (95% CI): 1·024 (1·001, 1·048); P = 0·042). In contrast, there was no association between the frequency of allergic reactions and the storage time of irradiated RBCs or between the age of non-irradiated RBCs and the frequency of non-allergic reactions. Prolonged storage of irradiated RBCs was associated with a significant increase in non-allergic transfusion reactions. Overall, the irradiated RBCs appeared to cause more non-allergic reactions compared with non-irradiated RBCs.

Dose-Dependent Effect of Stored Red Blood: Results of a Sub-Group Analysis of the Age of Blood Evaluation (ABLE) Trial

▪The red blood cell (RBC) storage lesion reflects cumulative damage to stored erythrocytes. Randomized clinical trials have yet to identify clinical consequences associated with prolonged RBC storage, however the majority of these trials have not incorporated dose-response analyses. In one of the subgroup analyses undertaken in the ABLE trial, a potential volume-dependent effect associated with storage was identified1.In this secondary analysis of the ABLE study, we conducted detailed analyses aiming to better characterize whether the number of RBC units administered to patients receiving either fresh or standard-issue blood is associated with mortality in critically-ill adults.We undertook a secondary evaluation of the 2510 patients enrolled in the ABLE trial. This randomized, controlled, clinical trial compared mortality rates and several secondary outcomes in mechanically-ventilated adults, who received either "fresh" RBC units (stored for ≤7 days) or "standard-issue" RBC units (first-in, first-out). Our secondary analysis consisted of comparing short- and long-term hazards of death between fresh and standard arms within pre-specified subgroups of patients that received ≤3 RBC units and those that received >3 units. Additional analyses using subgroups defined by 2-unit, and 1-unit increments were performed. Cox proportional hazards regression was used to model the hazard of death at the specified endpoints, adjusting for possible confounders. We examined interactions between randomization to fresh RBCs and number of RBC units transfused, as a means of establishing a dose-dependent relationship. We also undertook adjusted and unadjusted survival analyses between treatment arms within subgroups.In the subgroup that received ≤3 RBCs, there were 754 patients in the fresh arm and 789 in the standard arm; among patients transfused >3 RBCs, there were 457 in the fresh arm and 430 in the standard arm. When stratified by 2 unit increments, in the fresh and standard arms, respectively, there were 601 and 632 patients given ≤2 units, 279 and 272 given 3-4 units, 108 and 107 given 5-6 units, and 223 and 208 given ≥7 units.Baseline characteristics were comparable between treatment arms within major subgroups, aside from a slightly higher proportion of fresh RBC patients admitted due to trauma in the most transfused subgroups (>3 units: 11.4% of standard, 16.4% of fresh; ≥7 units: 11.5% of standard, 19.3% of fresh) and fewer patients admitted with medical causes in the same subgroups (>3 units: 77.7% of standard, 69.6% of fresh; ≥7 units: 77.9% of standard, 67.7% of fresh).There was significant interaction between fresh RBC unit transfusion and the volume of transfused RBC units on long-term (90 and 180 days) but not short-term (28-day, in-ICU, in-hospital) hazards of death for all subgroup analyses. This observation suggests that the effect of RBC storage differs with different transfusion volumes.In subgroups of ≤3 and >3 units, a trend was observed of increased hazard of death with fresh RBCs in the less-transfused subgroup, and decreased hazard of death with fresh RBCs in the more-transfused subgroup at all endpoints (Figure 1). Similar trends were observed with smaller RBC unit increments. At all endpoints, the hazard of death was higher with fresh RBCs in patients given 3-4 units and, after a threshold of 5 units, the trend reversed: patients given ≥7 fresh units had a lower hazard (Figure 2).Overall survival was not significantly different between treatment arms in any of the subgroups.This secondary analysis suggests a volume-dependent, threshold effect of prolonged red cell storage. Fresh RBCs were associated with a trend of decreased hazard of mortality when more than 5 units were transfused. The findings support current transfusion practice for patients requiring transfusion of <5 RBC units. Further study on the effect of RBC unit storage age should be focused on patients anticipated to require more than 5 RBC transfusions.The ABLE trial was funded by the Canadian Institutes of Health (grant #177453) and the Établissement français du sang. Dr. Mack is supported by a Fonds de recherche du Québec - Santé ’Resident Physician Health Research Career Training Program’ award.1. Lacroix J, Hébert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall JC, Clayton L, McIntyre L, Callum J, Turgeon AF, et al. Age of Transfused Blood in Critically Ill Adults. New England Journal of Medicine. 2015;372(15):1410-1418. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Rationale and Design of the Informing Fresh versus Old Red Cell Management (INFORM) Trial: An International Pragmatic Randomized Trial.

Although red blood cell transfusion is a potentially lifesaving intervention in severely anemic and acutely bleeding patients, some observational studies have suggested that prolonged red cell storage before transfusion is associated with harm. INFORM is a large, pragmatic, randomized controlled trial comparing the effect of the shorter storage with longer storage red blood cell transfusions on inhospital mortality in hospitalized patients who require a blood transfusion. The trial is being conducted in centers in Australia, Canada, Israel, and the United States and is expected to enroll 31497 patients. If the results of INFORM indicate that shorter storage red blood cell transfusion is associated with superior outcomes compared with standard issue red blood cell transfusion, consideration may be given to shortening blood storage times. If, in contrast, the INFORM trial provides no evidence of harm from longer storage red blood cells, clinicians and patients may be reassured that current blood inventory management strategies are appropriate.

Clinical effects of transfusing older red cell concentrates: an updated overview

The literature on possible effects of prolonged storage of red cells is growing fast. Recent studies still come up with conflicting results. This review describes some of the underlying mechanisms which may explain the opposing results from the different studies.

Does Prolonged Red Cell Storage Affect Outcomes in the Critically Ill?

Does Prolonged Red Cell Storage Affect Outcomes in the Critically Ill?

Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study

IntroductionWith prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused. The objective of this study was to determine if RBC transfusions or RBC storage age predicts incident DVT in medical or surgical intensive care unit (ICU) patients.MethodsUsing a database which prospectively enrolled 261 patients over the course of 1 year with an ICU stay of at least 3 days, we analyzed DVT and RBC transfusions using Cox proportional hazards regression. Transfusions were analyzed with 4 thresholds, and storage age using 3 thresholds. DVTs were identified by twice-weekly proximal leg ultrasounds. Multivariable analyses were adjusted for 4 significant DVT predictors in this population (venous thrombosis history, chronic dialysis, platelet transfusion and inotropes).ResultsOf 261 patients, 126 (48.3%) had at least 1 RBC transfusion; 46.8% of those transfused had ≥ 5 units in ICU. Patients receiving RBCs were older (68.8 vs 64.1 years), more likely to be female (47.0 vs 30.7), sicker (APACHEII 26.8 vs 24.4), and more likely to be surgical (21.4 vs 8.9) (P < 0.05). The total number of RBCs per patient was 1-64, mean was 6.3 (SD 7.5), median was 4 (IQR 2,8). In univariate analyses, there was no association between DVT and RBC exposure (1 day earlier, 3 days earlier, 7 days earlier, or ever) or RBC storage (≤ 7 or > 7 days, ≤ 14 or > 14 days, ≤ 21 or > 21 days). Among patients transfused, no multivariable analyses showed that RBC transfusion or storage age predicted DVT. Trends were counter to the hypothesis (e.g., RBC storage for ≤ 7 days suggested a higher DVT risk compared to > 7 days (HR 5.3; 95% CI 1.3-22.1).ConclusionsWe were unable to detect any association between RBC transfusions or prolonged red cell storage and increased risk of DVT in medical or surgical ICU patients. Alternate explanations include a lack of sufficient events or patients' interaction, between patient groups, a mixing of red cell storage times creating differential effects on DVT risk, and unmeasured confounders.

A Pilot Trial Evaluating the Clinical Effects of Prolonged Storage of Red Cells

The clinical consequences of prolonged storage of red cells have not been established. In this pilot study, we evaluated whether it would be feasible to provide a continuous supply of red cells stored <8 days. In addition, we examined the potential benefits attributed to "fresh" as compared to standard red cells in 66 critically ill and cardiac surgical patients. Nine patients were issued red cells but were not transfused. From the 57 remaining patients, the number of units transfused averaged 5.5 +/- 8.43 red cell units in the experimental group compared to 3.3 +/- 3.27 red cell units in the standard group (P = 0.25). The median storage time was 4 days in the experimental group compared to 19 days in the standard group (difference of 15 days; interquartile range of 12-16 days; P < 0.001). Overall, 73% of patients received red cells with storage times that corresponded to the treatment allocation more than 90% of the time. The group receiving red cells <8 days old tended to be older on average (68 +/- 8.54 yr versus 63 +/- 15.30 yr; P = 0.13) and have more comorbid illnesses (85% versus 65%; P = 0.09). In total, 27% of patients in the experimental group died or had a life-threatening complication as compared to 13% in the standard group (P = 0.31). There were no differences in prolonged respiratory, cardiovascular, or renal support after randomization (P > 0.05). A large clinical trial comparing red cell storage times is feasible and warranted given the limited available evidence.

Prolonged storage of red cells: the effect of pH, adenine and phosphate.

Prolonged storage of red blood cells (RBCs) at 4 degrees C results in decreased intracellular ATP levels with diminished posttransfusion survival. Meryman described a preservative medium, exceptional in its capacity to increase these intracellular levels during the first weeks of storage and later in maintaining adequate levels, for extended storage periods. We modified this medium, investigated its constituents, and found that its ATP-preserving effect was unrelated to its tonicity or to the presence of mannitol. Throughout storage, RBC potassium leakage and lactate production were moderate. No evidence of osmotic swelling was detected. In spite of high ATP levels, the cells became echinocytes, thus discounting a direct correlation between shape and metabolic status. The most striking finding in this study was that the prestorage pH of the blood unit (pH 7.0), has a crucial contribution in elevating nucleotide levels in a medium containing high levels of phosphate (18-40 mM) and adenine. We suggest that a combined effect of optimal pH, adenine, glucose and phosphate in the medium contributes to the ability of the RBCs to synthesize the necessary purine nucleotides by the 'salvage pathway'.

Prolonged Storage of Red Cells: The Effect of pH, Adenine and Phosphate

Prolonged Storage of Red Cells: The Effect of pH, Adenine and Phosphate

Prolonged storage of red cells with ammonium chloride and mannitol

Recently, a new preservation medium consisting of ammonium chloride added to adenine, glucose, mannitol, citrate, and potassium phosphate, was described. Unexpectedly, the predominant effect on red cell storage was an initial elevation of ATP levels, followed by remarkable maintenance of these levels at 12 to 18 weeks with acceptable 24-hour survival. The aim of the study reported here was to investigate the reasons for the advantageous effects of the different constituents. With the new preservation medium, ATP content was maintained at acceptable levels for at least 8 weeks with low spontaneous hemolysis. However, similarly high ATP levels were also maintained in the absence of ammonium chloride. Comparable results were obtained on substituting sodium for potassium salts in the new medium. When the main cation in the preservation medium was replaced by sodium, the addition of ammonium or rubidium chloride did not provide an advantage. Therefore, ammonium chloride was not essential for this medium, whereas mannitol does seem to be essential in a solution whose content of nonpermeant solutes is hypotonic.

Prolonged storage of red cells at 4 degrees C.

One of the events associated with red cell storage at 4 degrees C is the development of an increasing proportion of echinocytes. Vesicles also may bud off the spicules, presumably leading to a decreased surface-to-volume ratio and decreased deformability. Pursuing the hypothesis that increasing the surface tension of the cells by increasing their volume might reduce the tendency toward echinocytosis and extend refrigerated storage time, packed red cells were resuspended in a solution hypotonic (210 mOsm) with respect to solutes that do not penetrate the cell. Since a reduced ionic concentration results in increased membrane permeability for cations, normal ionic concentration was maintained by the addition of NH4C1, which readily penetrates red cells and therefore contributes no osmotic support. Adenine, glucose, mannitol, citrate, and phosphate also were included. Unexpectedly, the predominant effect of red cell storage in this solution was a remarkable elevation of adenosine triphosphate (ATP). At 4, 8, and 10 weeks, (ATP) levels averaged 165, 135, and 110 percent of initial values, respectively. At 16 weeks, ATP still averaged 50 percent of initial values. Twenty-four-hour in vivo survival of red cells measured at 12 to 18 weeks ranged between 70 and 80 percent, and hemolysis ranged from 0.3 to 7.1 percent. Both the hypotonicity and the ammonium salt appear to be necessary for the high ATP.