Abstract
In resource-limited settings and in the military theater, fresh human whole blood is commonly transfused, but infectious risks are a concern. Sophisticated molecular testing for potential infectious agents in the whole blood is often unavailable. To address this unmet need, pathogen reduction technology (PRT) has been developed, and it is an effective approach to inactivate a broad range of pathogens found in human blood. However, studies are needed to determine if it is harmful to blood cells and whether these cells could damage the transfused recipient, including the development of acute lung injury/acute respiratory distress syndrome. In this study, we used a commercial PRT system to treat human whole blood that was then transfused into immunodeficient mice, and the development of acute lung injury was determined. In a model of transfusion-related acute lung injury (TRALI), BALB/c SCID mice developed more robust lung injury when challenged with a MHC Class I monoclonal antibody compared to BALB/c wild-type and NOD/SCID mice. Transfusion of control versus Mirasol PRT-treated whole blood (25% blood volume exchange) into BALB/c SCID mice did not produce lung injury at storage day 1. However, mild lung injury at storage days 14 and 21 was observed without significant differences in lung injury measurements between Mirasol PRT-treated and control groups. The mild storage-dependent acute lung injury correlated with trends for increased levels of cell-free hemoglobin that accumulated in both the control and Mirasol PRT-treated groups. Neutrophil extracellular traps were elevated in the plasma of BALB/c SCID mice in the monoclonal antibody TRALI model, but were not different in mice that received exchange transfusions. In conclusion, exchange transfusion of human whole blood into immunodeficient mice produces mild lung injury that is storage-dependent and not related to pathogen reduction treatment.
Highlights
The safety of the blood supply has improved with the advent of modern transfusion therapy, a variety of pathogens, known and unknown, continue to provide risk to transfused recipients [1]
We examined whether human whole blood treated with Mirasol pathogen-reduction technologies (PRT) induces the development of neutrophil extracellular traps (NETs) [19] after exchange transfusion, since NETs are implicated in the pathogenesis of transfusion-related acute lung injury (TRALI) [20, 21]
The optical densities (OD) at 405nm and 490nm wavelengths were measured by plate reader and the difference between the two (OD405-490) was applied to a standard curve derived from bronchoalveolar lavage samples obtained from mice with acute lung injury to yield NET arbitrary units [22]
Summary
The safety of the blood supply has improved with the advent of modern transfusion therapy, a variety of pathogens, known and unknown, continue to provide risk to transfused recipients [1]. A prior study found that patients transfused with psoralen-based PRT of human platelet units had increased cases of the acute respiratory distress syndrome (ARDS), which may have been related to PRT-induced platelet activation [9] These cases of ARDS are akin to transfusionrelated acute lung injury (TRALI), which is the leading cause of transfusion-related death in many countries [10]. We tested Mirasol PRT, a technology that utilizes ultraviolet light illumination of human blood to which a photosensitizing agent, (riboflavin, vitamin B2) has been added [17]. This process creates nucleic acid modifications, which effectively inactivates a variety of pathogens. We examined whether human whole blood treated with Mirasol PRT induces the development of neutrophil extracellular traps (NETs) [19] after exchange transfusion, since NETs are implicated in the pathogenesis of transfusion-related acute lung injury (TRALI) [20, 21]
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