Transfusion Lung Injury (TRALI)

Transfusion related acute lung injury is acute hypoxaemic respiratory failure with bilateral pulmonary infiltrates that develops during transfusion or within 6 hours, not explained by left atrial hypertension. It is a leading cause of transfusion related death. It is under-recognised because it resembles other causes of respiratory failure in sick patients.

Case definition.

• Acute onset within 6 hours of transfusion.

• Hypoxaemia: ratio of arterial oxygen pressure to inspired oxygen fraction of 300 mmHg or less, or oxygen saturation under 90% on room air.

• Bilateral infiltrates on chest imaging.

• No evidence of left atrial hypertension, or, if present, it is not the main cause of the injury.

Type I. No risk factors for acute respiratory distress syndrome. Type II. Risk factors for acute respiratory distress syndrome present (sepsis, pneumonia, aspiration, surgery) or mild acute respiratory distress syndrome that is stable before transfusion. Cases that could be either TRALI or circulatory overload are labelled as such.

Mechanism. Donor antibodies (HLA class I or II, human neutrophil antigens) or biologically active lipids in stored products activate recipient neutrophils in the lung, a two hit process in which recipient inflammation (sepsis, surgery, trauma) primes the lung. Plasma and platelets (containing plasma) from multiparous women carry the highest risk. Red cells, cryoprecipitate and immunoglobulin products are involved less often.

Clinical features. Dyspnoea, cough, tachypnoea, hypoxia, fever, hypotension (often), frothy sputum and bilateral crepitations, usually within 1 to 2 hours.

Special groups. Critically ill patients, those with sepsis, haematological malignancy, cardiac surgery and massive transfusion are at higher risk.

Differential diagnosis.

• Transfusion associated circulatory overload (the most important difference).

• Acute respiratory distress syndrome from other causes, pneumonia and aspiration.

• Anaphylaxis, bacterial contamination with sepsis, and acute haemolytic reaction.

• Cardiogenic pulmonary oedema, pulmonary embolism and pneumothorax.

Distinguishing features from circulatory overload. Hypotension and fever favour lung injury, while hypertension, raised jugular venous pressure and a response to diuretics favour overload. A normal or low natriuretic peptide (a post-transfusion level under 1.5 times the pre-transfusion level) and normal left ventricular function and filling pressures on echocardiography support lung injury. Both can coexist.

Initial assessment. Oxygen saturation and arterial blood gas, chest imaging, bedside echocardiography where available, electrocardiogram, natriuretic peptide, blood cultures and review of fluid balance.

Immediate actions in order.

1. Stop the transfusion and clamp the line.

2. Assess the patient: airway, breathing (high flow oxygen), circulation, and call for senior and intensive care help.

3. Keep intravenous access with a new giving set and 0.9% sodium chloride.

4. Recheck identity of patient and unit.

5. Inform the blood bank and the responsible clinician at once, and return the unit and set.

6. Do not restart the transfusion.

Supportive treatment.

• Oxygen, non-invasive ventilation or intubation as required, with lung protective ventilation (tidal volume about 6 mL/kg ideal body weight, plateau pressure under 30 cmH2O).

• Fluids and vasopressors for hypotension, as pulmonary oedema in lung injury does not result from volume overload.

• Avoid diuretics unless circulatory overload also exists.

• Corticosteroids have no proven benefit.

Investigations.

• Chest imaging, arterial blood gas, natriuretic peptide, echocardiography, full blood count (transient leucopenia may occur), blood cultures and cultures of the product if septic.

• Blood bank investigation: HLA and human neutrophil antigen antibody testing in the donors of the implicated components, HLA and neutrophil antigen typing of the recipient, and crossmatch of donor serum against recipient cells.

• Quarantine of co-components from the same donations.

Definitive management. Supportive care, usually on intensive care. About 80% of patients improve within 48 to 96 hours, and mortality is about 5 to 10%. There is no specific treatment.

Further transfusion. If transfusion is needed, use products that are unlikely to contain implicated antibodies, and give only what is needed. In the donor, antibodies lead to deferral from donating plasma and platelets as the blood service decides.

Reporting. Report to the transfusion service and haemovigilance system as a serious reaction, with prompt donor investigation and recall of related components.

Prevention.

• Plasma for transfusion from male donors, or women tested negative for HLA antibodies, or pathogen reduced pooled plasma. Platelets with low plasma content or stored in additive solution.

• Avoid unnecessary transfusion, especially plasma and platelets, in critically ill patients.

• Recognise risk factors and use the lowest effective dose.