It is well documented that red cells undergo numerous, complex physical and chemical changes during refrigerated storage which impact on their function and survival. Although much is known about these changes, collectively known as the “red cell storage lesion”, there is still a lot that is not well understood.
In particular, the clinical relevance of these changes is not clear, prompting significant research and debate in this area. However, the results of studies undertaken to date have not been able to provide certainty of the clinical relevance. Whilst a number of clinical studies suggest that transfusion of older red cells is associated with poorer outcomes for patients compared with fresher red cell units, particularly in certain patient groups, other studies have not supported these findings. Additionally, most of the studies have been retrospective observational studies, not specifically designed to address the question of age of blood at transfusion, with multiple confounding variables to consider.
The US National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, has recently announced that it is funding nine research grants to determine if the safety and efficacy of red cell transfusions vary depending on how long the cells have been stored.
One of the grants supports the first large, multi-centre, randomised clinical trial to determine whether red cell storage time affects the postoperative outcomes of cardiac surgery patients. Participants of the Red Cell Storage Duration Study, or RECESS, will be randomly assigned to receive blood stored for 10 or fewer days, or blood stored for 21 or more days. Researchers will compare outcomes between the two groups, including mortality rates one month following surgery; post-operative complications such as stroke, heart attack, kidney failure, pulmonary embolism and sepsis; and the need for mechanical ventilation. RECESS plans to enrol about 1,830 patients, with most sites expecting to begin enrolling patients in early summer 2010, although additional sites may be added later. More information about the trial (NCT00991341) can be found at
http://clinicaltrials.gov/.
The other eight research grants will be used to fund eight different studies aimed at examining what changes red cell units undergo when they are prepared and stored, as well as whether those changes affect the blood vessels and tissues once transfused.
• "Storage lesion in banked blood due to disruption of nitric oxide homeostasis" This study, which proposes that transfusion damage from stored blood can be traced to reduced levels of nitric oxide, will investigate whether microparticles and free haemoglobin released from ruptured red cells in stored blood absorb nitric oxide.
• "RBC age and potentiation of transfusion related pathology in trauma patients" This study of injured patients in intensive care units who require red cell transfusion will investigate how red cell storage time affects capillary blood flow, and how this blood flow is affected by the interaction between banked blood and both nitric oxide and the immune system.
• "Adverse effects of RBC transfusions: A unifying hypothesis" This study will investigate how red cell storage time and preparation methods (including irradiation and leucodepletion) affect nitric oxide levels, blood flow and tissue oxygenation. It will also investigate whether patients with cardiovascular disease who have trouble making nitric oxide are more sensitive to the effects of stored and processed blood than fresh blood. More information about this clinical trial (NCT00838331) can be found at http://clinicaltrials.gov/.
• "Restoration and function of S-nitrosothiol in stored blood" This study will determine whether restoring S-nitrosohaemoglobin (SNO-Hb) levels in stored blood prior to transfusion will improve tissue oxygenation.
• "Identification and significance of biologic mediators in red cell concentrates" This study will investigate the supernatant of red cell units, including haemoglobin, microparticles and fats, to determine what changes it undergoes, what effects it and the stored red cells have on patients' platelets, and whether washing or other methods reverse those effects.
• "Microparticles in stored RBC as potential mediators in transfusion complications" This study will explore the role of red blood cell microparticles in transfusion complications including clotting, inflammation, immune suppression, and endothelial tissue disruptions. In addition, the researchers will compare results from transfused patients given either blood stored under standard conditions or blood that was washed to remove microparticles prior to storage.
• "Properties of stored RBCs: Minimisation of immune and vascular reactivity" This study will focus on the immune effects of stored versus fresh red cells, including the role of storage time on red cell-endothelial cell adhesion, microparticles and markers of inflammation, and a clinical study comparing immune and inflammatory responses in critically ill patients who receive either standard transfusions (no storage time specified) or red cells that have been stored for fewer than eight days.
• "Harmful effects of transfusion of older stored red cells: Iron and inflammation" This study will determine if iron, which is released after transfusion from damaged red cells that have been stored longer, triggers an intense inflammatory response that is particularly harmful to patients with haemoglobinopathies, such as sickle cell disease and beta-thalassemia.
Further information regarding this research is available at http://www.nih.gov/news/health/jun2010/nhlbi-21.htm
