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 (R(2) <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.

Conflict of interest statement

Conflict of interest: Nothing to report.

© 2015 Wiley Periodicals, Inc.

Figures

Figure 1

Histogram of RBC storage duration for the 100 RBC transfusions in the study. The median storage duration is 23 days (range 4–39 days).

Figure 2

RBC transfusions result in hemolysis and an acute phase response. The median with interquartile range for the change in serum levels of (A) indirect bilirubin, (B) serum iron, (C) non-transferrin-bound iron, (D) CRP, (E) free hemoglobin, and (F) haptoglobin from 4-hr after transfusion to pre-transfusion in the patients (N = 13) infused with both saline/albumin and transfused with RBCs at different times in their PICU admission. *P <0.05, **P <0.01.

Figure 3

RBC storage duration is a poor predictor of the extent of intra-vascular and extravascular hemolysis observed at 4-hr post-transfusion. A Spearman correlation was used to determine the relationship between the RBC storage duration and changes in circulating levels of (A) haptoglobin, (B) free hemoglobin, (C) indirect bilirubin, (D) serum iron, (E) non-transferrin-bound iron, and (F) hepcidin observed at 4-hr post-transfusion to pre-transfusion in patients (N= 100) transfused with RBCs. The P-values and Spearman correlation coefficient values are as specified in the Figure.

Figure 4

Measures of hemolysis are increased following transfusion of older, stored RBCs. The median with interquartile range for serum levels of (A) haptoglobin, (B) free hemoglobin, (C) indirect bilirubin, (D) serum iron, (E) non-transferrin-bound iron, and (F) hepcidin from 4-hr after transfusion to pre-transfusion in the patients infused with saline/albumin (N = 20) or transfused with RBCs stored for 0–14 days (N = 15; 1–2 weeks), 15–28 days (N= 65; 3–4 weeks), or 29–42 days (N= 20; 5–6 weeks). *P <0.05, **P <0.01, ***P <0.001 for the comparison to the saline/albumin control group.

Figure 5

RBC transfusion results in an acute phase response, predominantly in recipients exhibiting greater amounts of extravascular hemolysis. (A) A Spearman correlation was used to determine the relationship between the RBC storage duration and the change in CRP from 4-hr post-transfusion to pre-transfusion in patients (N= 100) transfused with RBCs. (B) The median with interquartile range for serum levels of CRP from 4-hr post-transfusion to pre-transfusion in patients infused with saline/albumin (N= 20) or transfused with RBCs stored for 0–14 days (N= 15; 1–2 weeks), 15–28 days (N= 65; 3–4 weeks), or 29–42 days (N= 20; 5–6 weeks). (C) The median with interquartile range for change in serum CRP levels in patients infused with saline/albumin (N= 20) or transfused with RBCs and with a change in indirect bilirubin of either <0.4 mg/dL (N= 79) or ≥0.4 mg/dL (N= 21). The P-values and Spearman correlation coefficient values are as specified in the figure, *P<0.05, **P<0.01.