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Background: Storage temperature is a critical factor for maintaining red-blood cell (RBC) viability, especially during prolonged cold storage. The target range of 1 to 6°C was established decades ago and may no longer be optimal for current blood-banking practices., Study Design and Methods: Human and canine RBCs were collected under standard conditions and stored in precision-controlled refrigerators at 2°C, 4°C, or 6°C., Results: During 42-day storage, human and canine RBCs showed progressive increases in supernatant non-transferrin-bound iron, cell-free hemoglobin, base deficit, and lactate levels that were overall greater at 6°C and 4°C than at 2°C. Animals transfused with 7-day-old RBCs had similar plasma cell-free hemoglobin and non-transferrin-bound iron levels at 1 to 72 hours for all three temperature conditions by chromium-51 recovery analysis. However, animals transfused with 35-day-old RBCs stored at higher temperatures developed plasma elevations in non-transferrin-bound iron and cell-free hemoglobin at 24 and 72 hours. Despite apparent impaired 35-day storage at 4°C and 6°C compared to 2°C, posttransfusion chromium-51 recovery at 24 hours was superior at higher temperatures. This finding was confounded by a preparation artifact related to an interaction between temperature and storage duration that leads to removal of fragile cells with repeated washing of the radiolabeled RBC test sample and renders the test sample unrepresentative of the stored unit., Conclusions: RBCs stored at the lower bounds of the temperature range are less metabolically active and produce less anaerobic acidosis and hemolysis, leading to a more suitable transfusion product. The higher refrigeration temperatures are not optimal during extended RBC storage and may confound chromium viability studies., (© 2018 AABB.)

Background and Objectives: Preclinical studies generated the hypothesis that older stored red blood cells (RBCs) can increase transfusion risks. To examine the most updated and complete clinical evidence and compare results between two trial designs, we assessed both observational studies and randomized controlled trials (RCTs) studying the effect of RBC storage age on mortality., Materials and Methods: Five databases were searched through December 2014 for studies comparing mortality using transfused RBCs having longer and shorter storage times., Results: Analysis of six RCTs found no significant differences in survival comparing current practice (average storage age of 2 to 3 weeks) to transfusion of 1- to 10-day-old RBCs (OR 0·91, 95% CI 0·77-1·07). RBC storage age was lower in RCTs vs. observational studies (P = 0·01). The 31 observational studies found an increased risk of death (OR 1·13, 95% CI 1·03-1·24) (P = 0·01) with increasing age of RBCs, a different mortality effect than RCTs (P = 0·02)., Conclusion: RCTs established that transfusion of 1- to 10-day-old stored RBCs is not superior to current practice. The apparent discrepancy in mortality between analyses of RCTs and observational studies may in part relate to differences in hypotheses tested and ages of stored RBCs studied. Further trials investigating 1- to 10-day-old stored RBC benefits would seem of lower priority than studies to determine whether 4- to 6-week stored units have safety and efficacy equivalent to the 2- to 3-week-old stored RBCs commonly transfused today., (© 2016 International Society of Blood Transfusion.)

Background: Massive exchange transfusion of 42-day-old red blood cells (RBCs) in a canine model of Staphylococcus aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin-bound iron (TBI), non-transferrin-bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs., Study Design and Methods: Two-year-old purpose-bred infected beagles were transfused with increasing volumes (5-10, 20-40, or 60-80 mL/kg) of either 42- or 7-day-old RBCs (n = 36) or 80 mL/kg of either unwashed or washed RBCs with increasing storage age (14, 21, 28, or 35 days; n = 40)., Results: All volumes transfused (5-80 mL/kg) of 42-day-old RBCs resulted in alike (i.e., not significantly different) increases in TBI during transfusion as well as in CFH, lung injury, and mortality rates after transfusion. Transfusion of 80 mL/kg RBCs stored for 14, 21, 28, and 35 days resulted in increased CFH and NTBI in between levels found at 7 and 42 days of storage. However, washing RBCs of intermediate ages (14-35 days) does not alter NTBI and CFH levels or mortality rates., Conclusions: Preclinical data suggest that any volume of 42-day-old blood potentially increases risks during established infection. In contrast, even massive volumes of 7-day-old blood result in minimal CFH and NTBI levels and risks. In contrast to the extremes of storage, washing blood stored for intermediate ages does not alter risks of transfusion or NTBI and CFH clearance., (© 2015 AABB.)

Background: In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects., Study Design and Methods: Two-year-old purpose-bred beagles (n = 12) were transfused similar quantities of either older (42-day) or fresher (7-day) stored universal donor canine RBCs 2.5 hours after undergoing controlled hemorrhage (55 mL/kg)., Results: With older transfused RBCs, CFH (p < 0.0001) and NTBI (p = 0.004) levels increased, but lung injury (p = 0.01) and C-reactive protein levels (p = 0.002) declined and there was a trend toward lower mortality (18% vs. 50%). All three deaths after transfused fresher RBCs resulted from hepatic fractures. Lowered exogenous norepinephrine requirements (p < 0.05) and cardiac outputs (p < 0.05) after older transfused RBCs were associated with increased CFH levels that have known vasoconstrictive nitric oxide scavenging capability., Conclusions: In hemorrhagic shock, older RBCs altered resuscitation physiology but did not worsen clinical outcomes. Elevated CFH may lower norepinephrine requirements and cardiac outputs ameliorating reperfusion injuries. With hemorrhagic shock, NTBI levels persist in contrast to the increased clearance, lung injury, and mortality in the previously reported infection model. These preclinical data suggest that whereas iron derived from older RBCs promotes bacterial growth, worsening septic shock mortality during infection, release of CFH and NTBI during hemorrhagic shock is not necessarily harmful., (© 2015 AABB.)

Purpose of Review: This article will analyze and evaluate the current evidence regarding the use of older, longer-stored red blood cells (RBCs) for transfusion in pediatric patients and will examine some of the postulated mechanisms of injury related to prolonged refrigerated storage of RBCs and studies reporting clinical outcomes., Recent Findings: Three randomized controlled trials and seven observational studies have been conducted entirely in pediatric patients. The outcomes, mortality and morbidity in critically ill patients and children undergoing cardiac surgery, and necrotizing enterocolitis in premature infants, have been inconsistent. However, many of these studies have been confounded by study design, mixed patient populations, red cell preparation, and other factors., Summary: Further exploration into the possible deleterious effects of older, longer-stored RBC transfusions on mortality and morbidity in different pediatric populations is merited. Understanding the potential mechanisms of injury should help explain the clinical findings.

Red blood cells (RBCs) degrade progressively during the weeks of refrigerated storage. No universally accepted definition of 'fresh' or 'old' RBCs exists. While practices vary from country to country, preservative solutions permitting shelf life as long as 7 weeks have been licenced. Transfusion of stored RBCs, particularly those at the end of the approved shelf life, has been implicated in adverse clinical outcomes. The results of observational analyses, animal models and studies in volunteers have proved provocative, controversial and contradictory. A recently completed randomized controlled trial (RCT) in premature infants exemplifies the difficulties with moderately sized clinical studies. Several other RCTs are in progress. The effect of RBC storage may well vary according to the clinical setting. Resolution of the importance of the storage lesion may require large pragmatic clinical trials. In the meantime, institutions involved in blood collection and transfusion should explore strategies that assure blood availability, while limiting the use of the oldest RBCs currently approved by regulation., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.