Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation.

Hod EA, Zhang N, Sokol SA, et al.
Blood 2010;115(21):4284-4292.
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Review by : L. T. Goodnough
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The authors used a mouse model to examine the effect of RBC transfusion on adverse outcomes related to free iron and inflammation. They hypothesized that acute clearance of damaged RBCs after prolonged storage delivers iron to the monocyte/macrophage system and induces inflammation. They demonstrated that transfusion of stored or washed RBCs increases plasma non-transferrin-bound iron (NTBI) and produces acute tissue iron deposition and initiates inflammation, compared to transfusion of fresh RBCs. They further demonstrated that membrane-encapsulated hemoglobin is required to produce inflammation; neither membrane ghosts nor stroma-free lysate derived from stored RBCs produced an inflammatory response.

The authors propose an “iron hypothesis” model to explain the mechanisms underlying the adverse events of stored RBC transfusions in their murine model:
1. An acute bolus of RBC-derived iron is delivered to the monocyte/macrophage system, resulting in oxidative stress and inflammatory cytokine secretion; and
2. Some of the macrophage-ingested iron is also released back into the circulation (NBTI), where it can cause oxidative damage and enhance bacterial proliferation.

The findings using this mouse model of RBC storage demonstrated adverse effects due to transfusion of older, stored RBC. The “iron hypothesis” advanced by the authors may also explain similar adverse effects seen in humans, if these are confirmed by prospective human clinical trials.

This is an important paper that significantly advances our understanding of the storage lesion of blood and its impact on adverse outcomes. If subsequent clinical trials demonstrate that prolonged storage of blood causes adverse outcomes compared to fresher blood, then inventory strategies for blood storage will need to be re-assessed, and alternatives to blood transfusion will undergo renewed emphasis.

Lawrence Tim Goodnough