Influence of eryptosis and storage on transfused red cell recovery in sepsis

Red blood cells (RBCs) are made in the bone marrow and circulate for four months. When donated blood is separated into its components, red cell concentrates (RCC) are made. RCC can be stored refrigerated for 6 weeks prior to transfusion. Soon after transfusion, many transfused RBC leave the patient’s circulation, and do not help the patient. Even more are lost when the RCC is aged (near its storage limit). Clinical research has shown that older RCC are as safe as fresher RCC, but it is not clear if the oldest RCC are effective. There is evidence that post-transfusion RBC losses are greater in the most critically ill patients. The storage limit may need to be reduced, so that the RCC blood product is of certain high quality. Improving RCC quality would mean that doctors could transfuse fewer units to achieve the same benefit for their patients, with fewer side effects. Why RCC do not last as long in storage as in people is not clear. Blood bank storage may speed up RBC aging. RBC in the circulation age gradually. RCC may undergo a different kind of aging called eryptosis. Eryptotic RBCs (eRBCs) are marked for rapid removal from the circulation. Previous research has shown that storage causes eRBC to form, as does a kind of critical illness called sepsis. We hypothesize that the combined effects of storage and sepsis are worse than the separate effects, and limit the quality and effectiveness of RCC. We will test this theory in four ways. Our first aim is to study eRBC formation when plasma, the liquid part of blood, from septic patients is combined with fresh or aged RBC from healthy donors. Our second aim is to use a mouse model of sepsis. We will compare how long fresh or aged RBC last when transfused to septic mice. Our third aim is to understand how fresh or aged RBC are recognized by the cells that remove them from the circulation. These cells are specialized white blood cells called monocytes or macrophages. We will study how these cells swallow and destroy fresh or aged RBC incubated with septic or normal plasma. Our fourth aim is to examine hospital records to see if aged RCC transfusion causes less of an increase in red cell count in septic patients. We will use a large database of hospital admission and transfusion data that houses tens of thousands of patient records. This research project will produce new knowledge about RCC blood product quality that could be used to make a better product. In the short term that improvement could come from limiting the storage limit to 5 weeks. In the long run we may be able to use this knowledge to design better additives to improve stored RBC quality and reduce adverse effects of RCC transfusion.

SHEFFIELD, William

McMaster University

Intramural Research Grant Program

Ontario

$283,569