The influence of the storage lesion(s) on pediatric red cell transfusion

Abstract

Further exploration into the possible deleterious effects of older, longer-stored RBC transfusions on mortality and morbidity in different pediatric populations is merited. Understanding the potential mechanisms of injury should help explain the clinical findings.

Mechanisms of red blood cell transfusion‐related immunomodulation

“…The RBC storage lesions are characterized by altered RBC morphology, rheologic changes, metabolic derangements, changes in oxygen affinity, changes in osmotic regulation, and changes in the ability to vasoregulate . In addition, RBC hemolysis (both during storage and after transfusion) can lead to reduced pH, increased lactate and other metabolic wastes, and release of microparticles as well as accumulation of cell‐free hemoglobin (Hb), heme, and iron . Iron content can be in the form of transferrin‐bound iron, non–transferrin‐bound iron (NTBI), or labile plasma iron.…”

“…Iron content can be in the form of transferrin‐bound iron, non–transferrin‐bound iron (NTBI), or labile plasma iron. Given the well‐described bioactivities of these species, RBC hemolysis can disturb plasma redox balance and broadly disrupt normal signaling in coagulation, vascular, and immune systems …”

“…Iron overload may also further promote immune suppression by impairing proliferation and activation of T, B, and NK cells . Additionally, independent of direct effects on immune cells, uncomplexed heme and iron may directly promote bacterial growth …”

“…Given the well-described bioactivities of these species, RBC hemolysis can disturb plasma redox balance and broadly disrupt normal signaling in coagulation, vascular, and immune systems. 4,22,23,78,86,91,92 In normal physiology, plasma haptoglobin sequesters cell-free Hb, forming a complex for removal by macrophages via CD163. 18,22,23,93 However, in critical illness, even moderate intravascular hemolysis may overwhelm plasma-binding capacity resulting in unbound extracellular Hb.…”

“…111 Additionally, independent of direct effects on immune cells, uncomplexed heme and iron may directly promote bacterial growth. 78,93,105 Finally, an additional compound of interest is ubiquitin, an intracellular regulatory protein present in a variety of cell types. RBCs carry large amounts of ubiquitin relative to other cell types, and extracellular ubiquitin has been found to accumulate in RBC unit supernatants during storage.…”