TRALI is defined by SHOT as acute dyspnoea (shortness of breath) with hypoxia and bilateral pulmonary infiltrates during or within 6 hours of transfusion, not due to circulatory overload or other likely causes. Blood components mainly implicated in TRALI are plasma rich products such as Fresh Frozen Plasma (FFP) though TRALI following transfusion with low plasma products such as red blood cells have been demonstrated.

H&I laboratory investigations of suspected cases of TRALI usually start with HLA and HNA antibody testing of all implicated female donors and implicated transfused male donors. HLA antibody screening and identification would likely be carried out by Luminex and HNA antibodies investigations by the flowcytometric Granulocyte Immunofluorescence Test (GIFT) and/or the Monoclonal Antibody Specific Immobilisation of Granulocyte Antigens (MAIGA) test.

The patients would be HLA class I and II and HNA typed to establish the presence of matching antigens for any antibodies that may be present. Crossmatching is no longer considered a requirement.

The pathogenesis of TRALI is considered to be related to the transfusion of donor HLA and/or HNA antibodies that recognise matching antigens in the recipient or the infusion of lipids and other biological response modifiers that accumulate during storage of blood components, leading to pulmonary neutrophil activation.

The lungs contain the largest pool of neutrophils in the body where they fulfil an important sentinel role in maintaining sterility. The evidence suggests direct binding of antibodies to the neutrophils results in cellular activation leading to degranulation and respiratory burst responses, which in turn damage pulmonary endothelium. Degranulation involves the release of cytokines and other proinflammatory substances. Granule release from neutrophils depends on activation of intracellular signalling pathways, including β-arrestins, the Rho guanosine triphosphatase Rac2, soluble NSF attachment protein (SNAP) receptors, the src family of tyrosine kinases and the tyrosine phosphatase MEG2.

Antibodies in the recipient are not considered to be a likely cause of TRALI in the leucodepletion era except for granulocyte transfusion. A two event hypothesis has been put forward to explain the neutrophil activation. The first event is the underlying condition of the patients (trauma, infection, surgery etc.) resulting in priming of neutrophils. The second event is the transfusion of blood products resulting in activation of the primed neutrophils.

Suspected cases of TRALI are treated by immediate cessation of transfusion and administration of Oxygen, followed by laboratory investigation.