the early 1900s blood transfusion emerged as a standard of clinical practice that was perceived as relatively free of risk . the value of blood transfusion was largely unchallenged until the early 1980s , when transfusion - related disease transmission , particularly hiv transmission , became a huge public health concern . adverse consequences of red blood cell ( rbc ) transfusion include the following : hemolytic and non - hemolytic transfusion reactions , transmission of infectious agents , transfusion of contaminated rbcs , and transfusion - mediated immunomodulation . the first indication that immune modulation secondary to allogeneic blood transfusion existed in humans was reported more than 25 years ago , when opelz and colleagues   observed improved renal allograft survival with pretransplant allogeneic rbc transfusions . more recently , opelz and coworkers   reported a clear improvement in renal allograft survival with allogeneic blood transfusion in addition to modern immunosuppressive therapy . moreover , allogeneic blood transfusion - associated immunosuppression has been associated with a decreased recurrence rate of spontaneous abortion in affected women   and a reduced clinical relapse rate in patients with chronic inflammatory bowel disease . it has also been argued that immunosuppressive effects of allogeneic blood transfusion might adversely affect the outcome of patients undergoing curative operation for malignancy . in addition , several clinical studies demonstrated that allogeneic transfusion is an independent risk factor for postoperative bacterial infections . although most emphasis has been placed on immune suppression following transfusion , it has become evident that proinflammatory effects may be important as well . cytokines and other inflammatory mediators have been shown to accumulate during storage of blood products . plasma from stored rbcs has been demonstrated to prime the oxidase system in neutrophils ( even if leukoreduced ) , delay apoptosis , and activate endothelial cells , setting the stage for neutrophil - mediated tissue destruction and organ failure . indeed , several investigators have identified blood transfusion as an independent risk factor for postinjury multiple organ failure ( mof ) . the advancement of transfusion medicine as a specialty has paralleled our ability to store blood ex vivo in its liquid state . as storage techniques have improved and extended the storage period up to 42 days , there has been a shift from focusing on maintaining rbc viability to including the quality of transfused rbcs as well . the ' storage lesion ' has been defined as the constellation of changes to the rbc that occur during storage , including metabolic , biochemical , and molecular changes , which eventually result in irreversible damage and ultimately limit the storage period . although the term traditionally has been restricted to corpuscular damage , recent evidence shows that a number of bioreactive substances accumulate in the medium during storage . selected changes characteristic of the storage lesion and their potential consequences are listed in table 1 . red blood cell storage lesion we have been particularly interested in the relationship between blood transfusion and neutrophil priming . silliman and coworkers   demonstrated that , during routine storage of whole blood and packed rbcs , agents were generated that significantly primed the nadph ( nicotinamide adenine dinucleotide phosphate , reduced form ) oxidase system . this effect was not significant until after 2 weeks of storage and was maximal by by the time all of the components were out of date . those authors subsequently showed that this effect was largely due to accumulation of proinflammatory lipids , in particular lysophosphatidylcholines . despite the relative wealth of data regarding the changes related to storage of blood products , evidence of clinical significance has been sparse . the relationship between these adverse effects and the age of transfused blood , however , has not been adequately studied . the immediate effectiveness of this therapy in increasing systemic oxygen uptake is questionable because storage depresses the ability of rbcs to deform as well as unload oxygen peripherally . because 2 , 3-diphosphoglycerate and deformability recover in vivo following transfusion , one would expect to see a delayed increase in systemic oxygen consumption after rbc transfusion . marik and sibbald , however , noted no improvement in systemic oxygen consumption for up to 6 hours after transfusion . moreover , those authors noted an unexpected decrease in gastric intramucosal ph ( measured by gastric tonometry ) following transfusion with blood stored for longer than 15 days . they suggested that transfusion of old , poorly deformable rbcs leads to microcapillary sludging and obstruction , resulting in gut ischemia . in light of the potential for stored rbc transfusion to adversely affect oxygen delivery and uptake , purdy and colleagues   studied the relationship between the age of transfused blood and survival in critically ill septic patients . the authors retrospectively studied 31 patients admitted to their intensive care unit with severe sepsis . the number of units of packed rbcs transfused and the age of each unit was determined using blood bank records . there was no difference between survivors ( n = 12 ) and nonsurvivors ( n = 19 ) in age , sex , intensive care unit length of stay , incidence of septic shock , acute physiology and chronic health evaluation ii score , or total number of packed rbcs transfused . nonsurvivors , however , were transfused with significantly older rbcs ( median 24 days versus 21 days in survivors ; p < 0.0001 ) . survivors were transfused with a greater proportion of rbcs that were less than 10 days old ( 85% ) , whereas nonsurvivors received a greater proportion of rbcs that were greater than 20 days old ( 76% ) . vamvakas and carven   investigated the association between the duration of storage of transfused rbcs and postoperative infection following coronary artery bypass graft surgery . they observed that the mean duration of storage of all transfused rbcs was a significant predictor of postoperative pneumonia and wound infection . age of transfused rbcs remained a significant predictor of postoperative infection after controlling for other known risk factors . blood transfusion has consistently been shown to be a major risk factor for postinjury mof . initially , transfusion requirement was thought to be a surrogate for injury severity , but multiple studies have demonstrated it to be a robust and independent predictor of postinjury mof . we previously demonstrated that old , but not outdated , packed rbc plasma primes neutrophils for superoxide production . furthermore , old blood plasma activates endothelial cells in a dose- and age - dependent fashion . the concordant activation of endothelial cells and priming followed by activation of neutrophils is crucial to the development of postinjury mof . to investigate the clinical relevance of these laboratory data , we performed a multivariate analysis of trauma patients who received transfusions to examine the effects of the age of stored blood on the development of postinjury mof . we observed that patients who developed mof received significantly older packed rbc units and , furthermore , that the age of the units was an independent predictor of mof . current evidence shows that metabolic , biomechanical , and molecular changes occur during the storage of blood products . changes in blood banking practice ( i.e. leukocyte reduction ) , clinical practice ( i.e. lower transfusion ' trigger ' , recombinant erythropoietin ) , and continued development of blood substitutes may facilitate avoidance of the adverse effects of allogeneic blood transfusion .
during the past 20 years , the perceived value of blood transfusions has changed as it has become appreciated that transfusions are not without risk . 
 red blood cell transfusion has been associated with disease transmission and immunosuppression for some time . 
 more recently , proinflammatory consequences of red blood cell transfusion have also been documented . 
 moreover , it has become increasingly evident that stored red blood cells undergo time - dependent metabolic , biochemical , and molecular changes . 
 this ' storage lesion ' may be responsible for many of the adverse effects of red blood cell transfusion . 
 clinically , the age of blood has been associated with multiple organ failure , postoperative pneumonia , and wound infection . 
 the relationship between age of blood and clinical adverse effects needs further study .