Transfusion-Related Acute Lung Injury

Transfusion related acute lung injury is acute hypoxemic respiratory failure with bilateral pulmonary infiltrates occurring within 6 hours of a transfusion, without cardiac failure explaining it. It is a leading cause of transfusion-related death. Incidence is about 1 in 5000 transfused patients (higher in critically ill and surgical patients), and mortality is 5 to 10%.

Mechanism is a two-hit process

• First hit: the patient's own condition (sepsis, surgery, trauma, massive transfusion, hematologic malignancy) primes neutrophils and activates the pulmonary endothelium
• Second hit: antibodies in the donor product (anti-HLA class I or II, anti-human neutrophil antigen) or bioactive lipids in stored products activate primed neutrophils

The result is capillary leak and alveolar flooding with a protein-rich fluid. Plasma-rich components (plasma, platelets, whole blood) carry the highest risk, and plasma from multiparous women carries more antibodies. Most patients recover within 48 to 96 hours, though ventilation is needed in over two thirds of cases. Complications: acute respiratory distress syndrome, shock, death and rare persistent lung injury.

• Sudden dyspnea, tachypnea, cough with frothy pink sputum, hypoxemia and cyanosis within 1 to 2 hours of the transfusion (and no later than 6 hours)
• Fever, chills, tachycardia and hypotension (a distinguishing feature, compared with hypertension in circulatory overload)
• Bilateral crackles and no evidence of elevated jugular venous pressure
• Transient fall in neutrophil and platelet count
• Red flags: saturation under 90% on room air, hypotension, and need for ventilation

1. Clinical diagnosis: acute onset hypoxemia (PaO2 to FiO2 ratio under 300 or saturation under 90% on room air), bilateral infiltrates on imaging, no evidence of left atrial hypertension (or if present, not the main cause), onset within 6 hours of transfusion, and no other acute lung injury risk factor.
2. Chest radiograph: bilateral alveolar infiltrates with a normal heart size.
3. Natriuretic peptide: BNP under 1200 pg/mL, or a ratio of post-transfusion to pre-transfusion value under 1.5, favors injury rather than circulatory overload.
4. Echocardiography: normal left ventricular function and filling pressures.
5. Pulmonary edema fluid to plasma protein ratio over 0.65 (an exudate) when sampled from the endotracheal tube.
6. Laboratory tests: full blood count (transient leukopenia), arterial blood gas, cultures.
7. Reporting and donor investigation: notify the blood service immediately, quarantine co-components from the donation, and test donor and recipient for HLA and neutrophil antibodies and cognate antigens.

Differentials: transfusion-associated circulatory overload, anaphylaxis, bacterial contamination of the product, hemolytic reaction, pneumonia, aspiration and acute respiratory distress syndrome of other cause.

1. Stop the transfusion immediately, keep IV access with 0.9% saline, and keep the bag and set for investigation.
2. Oxygen: high-flow oxygen, with non-invasive ventilation tried for mild cases. Intubate for refractory hypoxemia.
3. Lung-protective ventilation: tidal volume 6 mL/kg predicted body weight, plateau pressure under 30 cmH2O, positive end-expiratory pressure titrated to oxygenation, and prone positioning for a ratio under 150.
4. Hypotension: IV 0.9% saline 250 to 500 mL cautiously, and norepinephrine 0.05 to 0.5 micrograms/kg/min IV if needed. Avoid diuretics unless there is volume overload, since patients are often intravascularly depleted.
5. Corticosteroids have no proven benefit. Avoid routine use.
6. Refractory hypoxemia: neuromuscular blockade for a short period (cisatracurium 0.15 mg/kg IV bolus then 1 to 3 micrograms/kg/min) and venovenous extracorporeal membrane oxygenation.
7. Future transfusion: if an implicated donor is identified, defer that donor. Use plasma and platelets from male donors, or never-pregnant women, or plasma from donors tested negative for HLA antibodies, and washed or additive-solution platelets. Transfuse only when needed. Red cells can be given safely when indicated.
8. Children: the same approach with weight-based fluids (10 mL/kg boluses) and vasopressors.

Follow-up: chest imaging at 4 to 6 weeks if symptoms persist. Document the reaction in the patient record, and counsel the patient and the transfusing team on future precautions.