Red Blood Cell Storage in Transfusion-Related Acute Gut Injury

Abstract

Transfusion-related acute gut injury is defined as the occurrence of necrotizing enterocolitis 48 hours or less after a packed red blood cell (PRBC) transfusion for marked anemia in older, low-risk infants born at extremely low gestational ages (<28 weeks’ gestational age) who are no longer experiencing any historically associated risk factors except enteral feeding. As oxygen delivery decreases with advancing anemia, growing premature neonates compensate by redistribution of blood flow, increased cardiac output, and elevated oxygen extraction. Further adjustments to microvascular blood flow arise from nitric oxide–based hypoxic vasodilation, which eventually becomes limiting for sustaining oxygen consumption. Among many effects on red blood cells (RBC), storage lowers donor RBC nitric oxide content and increases free hemoglobin nitric oxide scavenging, whereas low oxygenation reduces nitric oxide production by endothelial nitric oxide synthase; these varied mechanisms collectively result in mitigation of hypoxic vasodilation. Because the adverse effect of packed RBCs on neonatal gut oxygenation appears primarily in association with extreme anemia, a sudden reduction in mucosal blood flow during periods of increased oxygen demand (enteral feeding) presumably results in injury to the physical barrier, enabling bacterial invasion and necrotizing enterocolitis. In infants born at extremely low gestational ages, PRBC transfusions for iatrogenic or developmentally acquired anemia are common and will persist even after all conservation techniques, microassay methods, and use of erythropoietin have been implemented. A fixed need for transfusions exists because of additional biologic restrictions imposed by normal rates of human somatic growth coupled with limits of RBC production to accommodate the need for an expanding RBC mass. Improved understanding of etiologic mechanisms of microvascular injury with transfusion should be instructive to clinicians in managing this dilemma.