Learning objectives

• Describe the risk factors and pathophysiology of TRALI
• Diagnose and manage TRALI
• Prevent TRALI

Background

• Transfusion-related acute lung injury (TRALI) is a transfusion reaction characterized by an acute, noncardiogenic pulmonary edema associated with hypoxia 
• The leading cause of death from transfusion 
• Caused by damage to pulmonary vasculature due to the immune response to antibodies or proinflammatory factors from the transfusion product that bind to antigens of the recipient
• Symptoms include acute dyspnea, fever, hypotension, and tachycardia

Risk factors

• Mechanical ventilation
• Sepsis
• Massive transfusion
• Coronary artery bypass graft
• End-stage liver disease
• Positive fluid balance
• Critically ill patient
• Blood products with high plasma contents

Pathophysiology

• Two-hit hypothesis:
  • First hit: Priming of neutrophils due to shock, sepsis, organ damage, previous surgery, stress, trauma
  • Second hit: Antibodies or proinflammatory factors in the transfusion product activate neutrophils, resulting in capillary leakage and subsequent pulmonary edema
• Threshold hypothesis
  • No first hit, a threshold must be overcome to induce TRALI
  • Threshold depends on the susceptibility of the patient and the quantity of antibodies/proinflammatory factors in the transfusion product

Diagnosis

• Diagnostic criteria: 
  • Symptoms develop during or within 6 hours of transfusion without any risk factors for developing acute lung injuries (sepsis from pneumonia, aspiration, shock)
• Clinical findings:
  • Exudative bilateral infiltrates on chest radiograph
  • No evidence of pulmonary vascular overload
  • Hypoxemia: SpO2 <90% on room air, ratio of partial oxygen pressure to fractional inspired oxygen concentration <300 mmHg
  • Possible TRALI: Other risk factors for acute lung injury
  • Delayed TRALI: 6 – 72 hours after transfusion

Differential diagnosis

• Septic transfusion reaction: Signs of sepsis
• Anaphylactic transfusion reaction: Laryngeal and bronchial edema
• Transfusion-related circulatory overload: Increased pulmonary artery occlusion pressure (>18 mmHg)

Treatment

• There is no treatment, management is supportive
• Stop transfusion
• Additional oxygen
• Restrictive tidal volume ventilation
• Diuretics may be considered

Prevention

Suggested reading

• Cho MS, Modi P, Sharma S. Transfusion-related Acute Lung Injury. [Updated 2022 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507846/
• Vlaar AP, Juffermans NP. Transfusion-related acute lung injury: a clinical review. Lancet. 2013;382(9896):984-994. 

Clinical updates

Kor et al. (Anesthesiology, 2025) investigate whether point-of-care washing of allogeneic red blood cells reduces biological markers associated with transfusion-related respiratory complications, including pathways implicated in TRALI. The study shows that RBC washing significantly reduces proinflammatory mediators, cell-free hemoglobin, and microparticles that are thought to contribute to neutrophil activation and endothelial injury in TRALI.