Transfusion-Related Acute Gut Injury: Feeding, Flora, Flow, and Barrier Defense

TRAGI (transfusion-related acute gut injury) is an acronym we proposed to characterize a severe neonatal gastrointestinal reaction temporally related to a transfusion of packed blood red cells (PRBCs) for anemia in very low birth weights. The following are in support of a causative relationship: (1) the timing of necrotizing enterocolitis after a PRBC transfusion not being random, (2) traditional risk factors for necrotizing enterocolitis are often absent, (3) significant anemia appears to be a universal finding, (4) the age of donor blood is often slightly older than controls, (5) TRAGI is not postnatal age dependent, and (6) TRAGI does not show a centering at 31 weeks' postconceptual age as does nontransfusion-related NEC. Although TRAGI is linked to the timing of PRBC transfusions, we propose a novel hypothesis that the convergence at 31 weeks' postconceptual age for classic NEC approximates the age of presentation of other oxygen delivery and neovascularization syndromes (eg, retinopathy of prematurity), suggesting its etiologic link to a generalized systemic maturational mechanism or another common developmental theme. This report will begin by reviewing the history of the clinical presentation and discovery of TRAGI and will then analyze various pathophysiologic mechanisms that may account for the phenomenon when clinicians render therapies. We will end by a call to action for randomized clinical trials to test various etiologic theories.