There is emerging evidence that platelets are major contributors to inflammatory processes through intimate associations with innate immune cells. Here, we report that activated platelets induce the formation of neutrophil extracellular traps (NETs) in transfusion-related acute lung injury (TRALI), which is the leading cause of death after transfusion therapy. NETs are composed of decondensed chromatin decorated with granular proteins that function to trap extracellular pathogens; their formation requires the activation of neutrophils and release of their DNA in a process that may or may not result in neutrophil death. In a mouse model of TRALI that is neutrophil and platelet dependent, NETs appeared in the lung microvasculature and NET components increased in the plasma. We detected NETs in the lungs and plasma of human TRALI and in the plasma of patients with acute lung injury. In the experimental TRALI model, targeting platelet activation with either aspirin or a glycoprotein IIb/IIIa inhibitor decreased NET formation and lung injury. We then directly targeted NET components with a histone blocking antibody and DNase1, both of which protected mice from TRALI. These data suggest that NETs contribute to lung endothelial injury and that targeting NET formation may be a promising new direction for the treatment of acute lung injury.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the US. Previously, we established an immune-mediated TRALI mouse model, wherein mice with cognate antigen were challenged with MHC class I mAb. In this study, when mice housed in a rodent, specific pathogen-free barrier room were challenged with MHC I mAb, there was significant protection from TRALI compared with nonbarrier mice. Priming mice with LPS restored lung injury with mAb challenge. Using TLR4-deficient bone marrow chimeras, the priming phenotype was restricted to animals with WT hematopoietic cells, and depletion of either neutrophils or platelets was protective. Both neutrophils and platelets were sequestered in the lungs of mice with TRALI, and retention of platelets was neutrophil dependent. Interestingly, treatment with aspirin prevented lung injury and mortality, but blocking the P selectin or CD11b/CD18 pathways did not. These data suggest a 2-step mechanism of TRALI: priming of hematopoietic cells, followed by vascular deposition of activated neutrophils and platelets that then mediate the severe lung injury. Furthermore, our data offer an explanation for the increased incidence of TRALI in patients with immune priming conditions, and we suggest what we believe to be a novel therapeutic approach.

CONTEXT CONTEXT Inaccurate and incomplete imaging order information presented to interpreting radiologists is a persistent problem in many radiology settings. Computerized Physician Order Entry processes in clinic-based settings are often inconsistent, and radiology transcription clerks continue to play a critical role in transmitting accurate content and information from referring physician orders to the radiology information system. (RIS) The purpose of this quality improvement project was to a) identify common transcription areas of deficient RIS imaging order information and b) test outcomes from an intervention to improve the content and concordance of transcribed patient information entered into the RIS. METHODS METHODS A random convenience sample of 500 outpatient radiographic orders were categorized according to degree and quality of concordance between the transcribed patient information documented in the RIS and the corresponding original imaging order information. During Phase I, the authors used a root-cause analysis to determine the possible etiologies for discordance between the information in original imaging orders and the information transcribed into the RIS. The intervention that was delivered included a short education session with radiology transcription clerks with placement reminder posters at transcription workstations. During Phase 2, a second random sample was obtained following the intervention, with data collection and analyses replicating the process from Phase I. A set of inferential comparisons were conducted using chi-square tests to examine for statistical significance. RESULTS RESULTS There was an overall 44% decrease in transcription discordance (p < 0.001), and the number of cases with perfectly concordant RIS order indication documentations increased by 21% (p < 0.001). A total of 34% of transcriptions from Phase I were partially discordant due to an inadequate imaging study indication, compared to 15% during Phase II (p < 0.001). There was also a 22% increase in the number of completely concordant transcriptions free of grammatical errors (p < 0.001). CONCLUSIONS CONCLUSIONS A short education session with radiology transcription clerks along with placement of reminder posters may significantly improve both the concordance and quality of transcribed imaging order information presented to interpreting radiologists using the RIS.

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