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Keywords:

  • animal models;
  • neutrophils;
  • platelets;
  • sheep;
  • TRALI;
  • two-event

Background and Objectives  Even with the introduction of specific risk-reduction strategies, transfusion-related acute lung injury (TRALI) continues to be a leading cause of transfusion-related morbidity and mortality. Existing small animal models have not yet investigated TRALI resulting from the infusion of heat-treated supernatant from whole blood platelet concentrates. In this study, our objective was the development of a novel in vivo two-event model of TRALI in sheep.

Materials and Methods  Lipopolysaccharide (LPS; 15 μg/kg) as a first event, modelled clinical infection. Transfusion (estimated at 10% of total blood volume) of heat-treated pooled supernatant from date-of-expiry human whole blood platelet concentrates (d5-PLT-S/N) was used as a second event. TRALI was defined by both hypoxaemia that developed either during the transfusion or within two hours of its completion and post-mortem histological evidence of pulmonary oedema.

Results  LPS infusion did not cause lung injury itself, but did result in decreased circulating levels of lymphocytes and neutrophils with evidence of the latter becoming sequestered in the lungs. Sheep that received LPS (first event) followed by d5-PLT-S/N (second event) displayed decreased pulmonary compliance, decreased end tidal CO2 and increased arterial partial pressure of CO2 relative to control sheep, and 80% of these sheep developed TRALI.

Conclusions  This novel ovine two-event TRALI model presents a new tool for the investigation of TRALI pathogenesis. It represents the first description of an in vivo large animal model of TRALI and the first description of TRALI caused by transfusion with heat-treated pooled supernatant from human whole blood platelet concentrates.