Experimental prestorage filtration removes antibodies and decreases lipids in RBC supernatants mitigating TRALI in vivo

Abstract

Key Points• TRALI may be induced by antibodies to HLA or HNA antigens or lipids, which accumulate during storage.• Prestorage experimental filtration of RBCs removes HLA and HNA antibodies, decreases lipid priming activity, and mitigates TRALI in an animal model.Transfusion-related acute lung injury (TRALI) remains a significant cause of transfusionrelated mortality with red cell transfusion. We hypothesize that prestorage filtration may reduce proinflammatory activity in the red blood cell (RBC) supernatant and prevent TRALI. Filters were manufactured for both small volumes and RBC units. Plasma containing antibodies to human lymphocyte antigen (HLA)-A2 or human neutrophil antigen (HNA)-3a was filtered, and immunoglobulins and specific HNA-3a and HLA-2a neutrophil (PMN) priming activity were measured. Antibodies to OX27 were added to plasma, and filtration was evaluated in a 2-event animal model of TRALI. RBC units from 31 donors known to have antibodies against HLA antigens and from 16 antibody-negative controls were filtered. Furthermore, 4 RBC units were drawn and underwent standard leukoreduction. Immunoglobulins, HLA antibodies, PMN priming activity, and the ability to induce TRALI in an animal model were measured. Small-volume filtration of plasma removed >96% of IgG, antibodies to HLA-A2 and HNA-3a, and their respective priming activity, as well as mitigating antibodymediated in vivo TRALI. In RBC units, experimental filtration removed antibodies to HLA antigens and inhibited the accumulation of lipid priming activity and lipid-mediated TRALI. We conclude that filtration removes proinflammatory activity and the ability to induce TRALI from RBCs and may represent a TRALI mitigation step. (Blood. 2014;123(22):3488-3495)

Storage of Red Blood Cells and Transfusion-Related Acute Lung Injury

“…When comparing aged RBC supernatant with aged but washed RBCs in LPS-primed animals, aged supernatant lead to increase of both inflammation and coagulopathy markers in a two-event TRALI model [31]. In a "two-hit" rat model pre-treated with either saline or LPS, filtration of plasma containing 50 µg/ml of antibodies OX27 prior to infusion inhibited TRALI compared to unfiltered plasma which resulted in lung injury [32].…”

Spotlight on pathogenesis of TRALI: HNA-3a (CTL2) antibodies

“…In a murine model of HNA-3a antibody-induced TRALI, these filters resulted in reduced neutrophil activation and prevention of lung injury. 31 By showing that prevention of neutrophil priming with filtration reduces acute lung injury, the study provides further support to a PMN-dependent model.…”

“…17 Most recently, experimental filters have shown efficacy in mitigating TRALI attributable to HNA antibodies (Figure 1). Silliman et al 31 describe a filtration system based on Pall BPF4 leukoreduction filters that depletes both antibodies and biological response modifiers from the red blood cell products. In a murine model of HNA-3a antibody-induced TRALI, these filters resulted in reduced neutrophil activation and prevention of lung injury.…”

Lesión pulmonar aguda tras transfusión de concentrado de hematíes en el paciente pediátrico. Presentación de caso y revisión de la literatura

“…Por otro lado, se han desarrollado filtros que absorben anticuerpos y lípidos que podrían mitigar el riesgo de TRALI, pero de momento sólo se ha demostrado su eficacia en modelos animales 17 . Si en un futuro se confirmaran estos datos en humanos, también habría que valorar coste beneficio de la implementación de esta medida en la práctica habitual.…”