Prolonged red cell storage before transfusion increases extravascular hemolysis

Abstract

NIH grant HL115557 and UL1 TR000040.

Iron accelerates hemoglobin oxidation increasing mortality in vascular diseased guinea pigs following transfusion of stored blood

“…Consistent with these findings, we observed maximum plasma NTBI concentrations in our model within the first 3 hours after S-RBC administration, with levels slowly declining over a 24-hour period. Posttransfusion increases in Tf saturation and subsequent hepcidin elevation appear not to be sufficient to control excess iron in circulation (21). We have therefore investigated if administration of apo-Tf might control NTBI accumulation in this situation.…”

“…In animals, these processes are reported to deregulate vascular nitric oxide (NO) homeostasis (15)(16)(17), promote inflammation (12), and exacerbate infection (18,19). In humans, posttransfusion saturation of transferrin (Tf) increases and NTBI accumulates in plasma as a result of extravascular hemolysis, taking place in the spleen and liver (20,21). As the number of RBC units administered increases, depletion of haptoglobin (Hp) levels leads to accumulation of cell-free Hb in plasma (22).…”

Transfusion-related immunomodulation: a reappraisal

“…In addition, although they hypothesized that the mechanisms underlying these results were due to classical immunological mechanisms, such as those involving T, B, and/or NK cells, other explanations are possible. For example, it is plausible that circulating non-transferrin bound iron (NTBI), which is produced in animal and human recipients following stored RBC transfusions [31–33], could cause endothelial cell damage [34–36], thereby increasing capillary permeability and enhancing endothelial cell adhesion molecule expression [37, 38]; thus, this effect on nutritional immunity could conceivably enhance circulating tumor cell “retention” in the pulmonary capillary bed. Alternatively, if this mechanism were true, one could conceivably propose that the effects of NTBI had nothing to do with nutritional immunity and, instead, were simply due to its direct toxic effects on endothelial cells.…”

“…Erythrophagocytosis, followed by lysosomal catabolism of the ingested RBCs, can rapidly produce NTBI [31–33], induce the release of specific cytokines [31], inhibit subsequent macrophage function, and damage lysosomes, potentially leading to cell death [40, 41]. In this context, macrophage cell death may have an “immunosuppressive” effect on innate immunity by decreasing the number of available phagocytes.…”

Haem is associated with thrombosis in neonates and infants undergoing cardiac surgery for congenital heart disease

“…Whether this threshold limit should be adjusted is currently under debate [2]. Haemolysis in vivo occurs immediately after transfusion of 'older' (longer storage duration) red cells into the recipient, and can be interpreted as a marker of impaired recovery of transfused red cells [3].…”