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Targeting Transfusion-Related Acute Lung Injury: The Journey From Basic Science to Novel Therapies

Semple, John W. PhD1–5; McVey, Mark J. MD1–3,6,7; Kim, Michael BSc1–2; Rebetz, Johan PhD5; Kuebler, Wolfgang M. MD1,8,9; Kapur, Rick MD, PhD5

doi: 10.1097/CCM.0000000000002989
Online Review Articles

Objectives: Transfusion-related acute lung injury is characterized by the onset of respiratory distress and acute lung injury following blood transfusion, but its pathogenesis remains poorly understood. Generally, a two-hit model is presumed to underlie transfusion-related acute lung injury with the first hit being risk factors present in the transfused patient (such as inflammation), whereas the second hit is conveyed by factors in the transfused donor blood (such as antileukocyte antibodies). At least 80% of transfusion-related acute lung injury cases are related to the presence of donor antibodies such as antihuman leukocyte or antihuman neutrophil antibodies. The remaining cases may be related to nonantibody-mediated factors such as biolipids or components related to storage and ageing of the transfused blood cells. At present, transfusion-related acute lung injury is the leading cause of transfusion-related fatalities and no specific therapy is clinically available. In this article, we critically appraise and discuss recent preclinical (bench) insights related to transfusion-related acute lung injury pathogenesis and their therapeutic potential for future use at the patients’ bedside in order to combat this devastating and possibly fatal complication of transfusion.

Data Sources: We searched the PubMed database (until August 22, 2017).

Study Selection: Using terms: “Transfusion-related acute lung injury,” “TRALI,” “TRALI and therapy,” “TRALI pathogenesis.”

Data Extraction: English-written articles focusing on transfusion-related acute lung injury pathogenesis, with potential therapeutic implications, were extracted.

Data Synthesis: We have identified potential therapeutic approaches based on the literature.

Conclusions: We propose that the most promising therapeutic strategies to explore are interleukin-10 therapy, down-modulating C-reactive protein levels, targeting reactive oxygen species, or blocking the interleukin-8 receptors; all focused on the transfused recipient. In the long-run, it may perhaps also be advantageous to explore other strategies aimed at the transfused recipient or aimed toward the blood product, but these will require more validation and confirmation first.

1Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, Canada.

2The Toronto Platelet Immunobiology Group, St. Michael’s Hospital, Toronto, ON, Canada.

3Canadian Blood Services, Toronto, ON, Canada.

4Departments of Pharmacology, Medicine, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

5Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden.

6Departments of Anesthesia and Physiology, University of Toronto, Toronto, ON, Canada.

7Department of Anesthesia and Pain Medicine, Sickkids Hospital, Toronto, ON, Canada.

8Department of Surgery and Department of Physiology, University of Toronto, Toronto, ON, Canada.

9Institute of Physiology, Charité-Universitätsmedizin, Berlin, Germany.

Drs. Semple and McVey contributed equally.

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Supported, in part, by grants from the Swedish Research Council, the Swedish Government Funds for Clinical Research, the Crafoord Foundation (to Dr. Semple), and the Canadian Institutes of Health Research and Canadian Blood Services (CBS) (to Drs. Semple and Kuebler) and additionally by a CBS Graduate Research Fellowship (to Dr. McVey).

Drs. Semple and Kapur’s institutions received funding from Health Canada Canadian Blood Services (CBS). Dr. Semple received support for article research from Health Canada and CBS. Dr. Kapur disclosed that he was previously supported by a postdoctoral fellowship from CBS. The remaining authors have disclosed that they do not have any potential conflicts of interest

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