The red blood cell storage lesion: the end of the beginning

The red blood cell (RBC) storage lesion refers to the series of biochemical, metabolic, and structural changes that occur when RBCs are stored ex vivo. A century has passed since the development by Rous and Turner of the first solution permitting rabbit RBCs biopreservation and their accurate prediction that “The indications are that kept human cells could be profitably employed in the same way. ” Since the demonstration that transfusion of stored whole blood saved lives in World War I, key advances in RBC biopreservation have included the development of several anticoagulant and additive solutions (ASs), controlled refrigeration, and sterile disposable plastic bags that allow RBC components to be stored and available to patients in need for up to 42 days in the United States. Food and Drug Administration (FDA) requirements are few and, in brief, include demonstrating that on average at 42 days of storage, more than 75% of autologous RBCs survive 24 hours in vivo when transfused back to healthy donors and that there is less than 1% hemolysis in the bag. These particular variables that were developed before clinical outcome studies of RBCs of different storage age were performed do not speak to the nature of the storage lesion elements and quality of RBCs nor to the effectiveness of RBC transfusions in different patient populations. The presence of the RBC storage lesion underlies the two major concerns regarding stored RBCs: efficacy and safety. Are transfusions of RBCs that have been stored for a longer period less effective at tissue oxygenation and CO2 removal than transfusion of units that have been stored for shorter periods? And are transfusions of RBCs that have been stored for a longer period associated with more clinical adverse effects than their “fresher” counterparts? These questions and resulting body of research have also led to a third distinct question: Is there room for improvement? In other words, can RBC transfusions of any storage duration be improved to enhance their therapeutic effectiveness and decrease potential adverse events and how is that best evaluated? The consideration that transfusion of longer-stored RBCs could potentially be associated with poorer outcomes was brought to the forefront by several observational studies including a large retrospective study by Koch and colleagues, which reported increased in-hospital mortality and morbidity (in particular sepsis) in patients who had undergone cardiovascular surgery and were transfused with RBC units that had been stored for more than 14 days (compared to patients receiving RBC units stored for 14 days). These results raised major concerns, and combined with a review of existing information, led the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) to substantially strengthen its support of basic, translational, and clinical research in this area. The importance of further characterizing the storage lesion defects, their reversibility in vivo, and their interaction(s) with the host, as well as the value of conducting randomized clinical trials to evaluate if RBC storage duration adversely affected patient outcomes were underscored by Glynn in 2010. A subsequent TRANSFUSION minisymposium highlighted the NHLBI