The current SHOT definition of transfusion‐related acute lung injury (TRALI) is as follows:

The pathophysiology of TRALI is not completely understood and is thought to be complex (Bolton‐Maggs [27], Semple et al. [250]). The model that is proposed is a ‘two‐hit model’ whereby an existing clinical pathophysiology has already caused neutrophils to sequest in the pulmonary capillaries and then a second hit is caused by the transfusion, whereupon a substance in the transfused component causes the neutrophils to activate (Semple et al. [250], Skeate and Eastlund [259]). The 2017 SHOT report cited plans for a future workshop to address some of the gaps in knowledge regarding transfusion pulmonary complications (Bolton‐Maggs [27], p.142). A new consensus definition was published in 2019 with new terminology to define TRALI (Vlaar et al. [279]). The new consensus definition is dependent on the presence or absence of existing risk factors for acute respiratory distress syndrome (ARDS) in the patient prior to transfusion. In type 1 TRALI, the patient has no risk factors for ARDS but following transfusion develops acute‐onset hypoxaemia with clear evidence of bilateral pulmonary oedema and no evidence of left anterior hemiblock, and this occurs within 6 hours of the end of the transfusion. Patients who have risk factors for ARDS or who have mild existing ARDS, but where the transfusion causes respiratory deterioration, are classified as type 2 TRALI (Vlaar et al. [279]).

TRALI is usually caused by antileucocyte antibodies reacting against donor leucocytes but there have been cases of TRALI that are antibody negative, and definitions of TRALI are shaped by the presence or absence of antibodies in serological testing (Bolton‐Maggs [27]). In many cases, either HLA or neutrophil‐specific antibodies were detected in the donors and most of the donors were multiparous (having been pregnant with one or more children) women. As the antibodies were mostly found in multiparous women and, as because SHOT reports demonstrate that in the majority of cases the donor is female, in 2003 NHSBT developed a strategy to use only the plasma from male donors for FFP and male plasma in pooled platelets (Bolton‐Maggs [27]).

TRALI is usually treated the same way as any ARDS and therefore patients who develop TRALI may require ventilatory support (Tinegate et al. [270]) and should be treated as emergency cases. Diuretics should not be administered as patients are generally hypotensive and hypovolaemic. As TRALI is donor related, it is essential that cases are reported to the blood transfusion services so that donors can be contacted, investigated for antibodies to HLA and, if necessary, removed from the donor panel (Norfolk [202]). The consensus committee emphasized that clinicians should report all cases of post‐transfusion pulmonary oedema to the transfusion service so that further investigation can take place (Vlaar et al. [279]).

Circulatory overload can occur when blood or any of its components is infused rapidly or administered to a patient with an increased plasma volume, causing hypervolaemia. Patients at risk are those with renal or cardiac deficiencies, the young and the elderly. Patients with signs of cardiac failure should receive their transfusion slowly with diuretic support (Norfolk [202]). A key recommendation of Narayan ([172]) is that all patients must be risk assessed for TACO as part of the decision to transfuse. Patients at risk of TACO must be closely monitored and then reassessed after each pack of blood component.

‘TAD is characterised by respiratory distress within 24 hours of transfusion that does not meet the criteria for TRALI, TACO or allergic reaction’ (International Society of Blood Transfusion cited in Narayan [172]). In these cases, the patient's underlying condition should not provide an adequate explanation for their respiratory distress.