Red blood cell storage and transfusion-related immunomodulation.

Abstract

Red blood cell (RBC) transfusion is a life-saving treatment for patients suffering severe blood loss or anaemia due to trauma injury, surgery, haemorrhage, haematological disease or malignancy. RBCs for transfusion are stored refrigerated in a preservative solution, which extends their shelf-life. Most of the preservative solutions in common use, such as saline-adenine-glucose-mannitol (SAG-M), enable refrigerated storage of RBCs for up to 42 days following collection. This expiry is based on criteria set by the United States of America Food and Drug Administration, which requires that 75 percent of transfused RBCs must be recoverable in the peripheral blood circulation 24 h after transfusion1. During refrigerated storage of RBC units, the RBCs undergo numerous physicochemical changes, collectively referred to as the RBC storage lesion, which affects the quality, function and in vivo survival of the transfused RBCs2–4. The implications for the transfusion recipient of these storage-related changes to RBCs are currently a matter of considerable interest and debate in the clinical community. In addition to their primary function to transport oxygen from the lungs to the tissues, RBCs are important regulatory components of haemorheology, the dynamics of blood flow5,6. In doing so, RBCs interact with the other blood elements, including white blood cells (WBCs), platelets and vascular cells. Many of the physical changes that occur to stored RBCs appear to be similar to those that occur to diseased RBCs (such as in malaria, sickle cell disease, thalassemia), in which disturbances of vascular function are key morbidities7,8. These changes include altered membrane surface receptors and cytoskeletal structures, which control RBC shape, flexibility (deformability) and aggregability. Knowledge gained from the study of diseased RBCs may provide insight into understanding the effect of storage on normal healthy RBCs and how these changes could influence the interaction of transfused RBCs with the recipient’s own cells and tissues. Transfusion-related immunomodulation (TRIM) has emerged as a concept to potentially explain numerous clinical observations that suggest that RBC transfusion is associated with increased proinflammatory or immunosuppressive effects that may increase morbidity in at least some patient groups9,10. The predominant mechanism of TRIM is likely to depend on an interplay of transfusion effects with the genetic predisposition and the intercurrent illnesses in the patient. Platelets and vascular endothelial cells also potentially contribute to the “response” as both cell types are highly responsive to inflammatory signals and when activated, release significant quantities of potent bioactive mediators. Thus, in situations of heightened inflammation or breach of vascular integrity, the immune and thrombotic systems are likely to be intricately linked in a complex network of signalling and response. This article aims to provide a perspective of the potential relationship between the RBC storage lesion and the concept of TRIM in its broader sense along with a brief overview of some of the research findings that could support this perspective. The role of proteomics in advancing our understanding of the RBC storage lesion as well as to provide insight into the biological mechanisms of TRIM is also discussed.