Editor's ChoiceTransfusion Complications

Keys to Safer Transfusions

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Science Translational Medicine  14 Oct 2009:
Vol. 1, Issue 2, pp. 2ec5
DOI: 10.1126/scitranslmed.3000366

More than 5 million people receive life-saving blood or platelet transfusions each year in the United States. Of these, about 5000 experience a severe complication—transfusion-related acute lung injury—which causes swelling in the lungs and sometimes death. Less healthy patients seem to be more susceptible and there is an immune component, but the exact cause of this serious side-effect has not been clear. On the basis of some surprising results, Looney et al. propose that this lung injury is caused by a two-step process in which an immune priming event is followed by sequestration of cells in the lungs and subsequent injury. In previous work, these authors treated mice with antibody to the immune protein MHC I, causing a mouse version of transfusion-related acute lung injury, with 50% mortality. In the new work, they repeated these experiments, but this time in highly controlled, completely clean, pathogen-free mouse housing. Unexpectedly, in this pristine environment, MHC I injection did not cause lung injury. Stimulating the immune system of the mice (with lipopolysaccharide from bacteria) before giving the MHC I in pathogen-free quarters restored its ability to cause lung injury, demonstrating that lung injury does not occur unless the immune system is primed first. In the second step of the two-step injury process, neutrophils and platelets accumulated in the lungs, as they do in patients and MHC I-injected mice in conventional housing. The neutrophils took up residence first, but did not cause lung damage by themselves. Platelets aggregated on the neutrophils (Depletion of the neutrophils prevented platelet buildup.) and were responsible for the acute lung injury. If the platelet aggregation in the lung was prevented with aspirin, the lungs remained healthy. Thus, a better understanding of the immune triggers of transfusion-related acute lung injury plus exploration of therapeutic approaches targeted to platelets should help to minimize the risk of this dangerous complication.

M. R. Looney et al., Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. J. Clin. Invest. (October 5, 2009) [doi:10.1172/JCI38432]. http://www.jci.org/articles/view/38432

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