Red blood cell transfusion is associated with increased hemolysis and an acute phase response in a subset of critically ill children

Abstract

In healthy adults, transfusion of older stored red blood cells (RBCs) produces extravascular hemolysis and circulating non-transferrin-bound iron. In a prospective, observational study of critically ill children, we examined the effect of RBC storage duration on the extent of hemolysis by comparing laboratory measurements obtained before, and 4 hr after, RBC transfusion (N=100) or saline/albumin infusion (N=20). Transfusion of RBCs stored for longer than 4 weeks significantly increased plasma free hemoglobin (P<0.05), indirect bilirubin (P<0.05), serum iron (P<0.001), and non-transferrin-bound iron (P<0.01). However, days of storage duration poorly correlated (R2<0.10) with all measured indicators of hemolysis and inflammation. These results suggest that, in critically ill children, most effects of RBC storage duration on post-transfusion hemolysis are overwhelmed by recipient and/or donor factors. Nonetheless, we identified a subset of patients (N=21) with evidence of considerable extravascular hemolysis (i.e., increased indirect bilirubin ≥0.4 mg/dL). In these patients, transfusion-associated hemolysis was accompanied by increases in circulating non-transferrin-bound iron and free hemoglobin and by an acute phase response, as assessed by an increase in median C-reactive protein levels of 21.2 mg/L (P<0.05). In summary, RBC transfusions were associated with an acute phase response and both extravascular and intravascular hemolysis, which were independent of RBC storage duration. The 21% of transfusions that were associated with substantial hemolysis conferred an increased risk of inducing an acute phase response.