What is the suspected mechanism of Transfusion-Related Acute Lung Injury (TRALI)?

Mechanism of Transfusion-Related Acute Lung Injury (TRALI)

TRALI is primarily caused by immune reactivity of leukocyte antibodies that interact with recipient antigens, resulting in neutrophil activation, endothelial damage, and non-cardiogenic pulmonary edema within hours of transfusion. 1, 2

Pathophysiologic Mechanisms

Antibody-Mediated Pathway

• TRALI is most commonly caused by donor antibodies (anti-leukocyte antibodies) in transfused blood products that react with white blood cell antigens of the recipient 2, 3
• Both Human Leukocyte Antibodies (HLA Class I and II) and Human Neutrophil Antibodies (HNA) are implicated in immune-mediated TRALI 3
• Signs and symptoms appear 1-2 hours after transfusion and reach maximum intensity within 6 hours 1
• Approximately two-thirds of TRALI cases are thought to be immune-mediated 3

Multiple Pathways of Development

• At least six different pathways have been identified in antibody-mediated TRALI 4:
  • Two-hit neutrophil activation (priming of neutrophils by underlying condition followed by antibody activation) 4, 5
  • Monocyte and neutrophil dependent pathway 4
  • Endothelial cell, neutrophil Fc receptor, platelet and neutrophil extracellular trap dependent pathway 4
  • Direct monocyte activation pathway 4
  • Direct endothelial cell activation pathway 4
  • Endothelial cell, complement and monocyte dependent pathway 4

Key Cellular Mechanisms

• Antibody-mediated neutrophil activation appears to be a critical trigger for TRALI 5
• Activated neutrophils release reactive oxygen species (ROS) that damage pulmonary endothelium 4, 5
• The final common pathway in all proposed mechanisms is increased pulmonary capillary permeability, resulting in plasma movement into alveolar spaces causing pulmonary edema 6

Risk Factors and Blood Product Considerations

• Multiparous donors have the highest incidence of leukocyte antibodies due to allo-exposure during pregnancy 3
• Fresh frozen plasma (FFP) has been identified as the blood component with the highest risk for causing TRALI due to its high plasma volume and potential for containing leukocyte antibodies 2
• While donor antibodies are most common, recipient anti-donor HLA or HNA antibodies have rarely been implicated in "reverse TRALI" 7

Clinical Presentation and Diagnosis

• Clinical features include hypoxemia, fever, dyspnea, and fluid in the endotracheal tube 1, 2
• TRALI is non-cardiogenic pulmonary edema, distinguishing it from transfusion-associated circulatory overload (TACO) 1, 2
• Most patients recover within 96 hours, although TRALI is one of the top three most common causes of transfusion-related deaths 1

Management

• No specific therapy exists other than stopping transfusion and instituting critical care supportive measures 1
• Diuretics are ineffective for TRALI (unlike TACO) and should be avoided 2
• Oxygen therapy and supportive care are the mainstays of treatment 2

Prevention Strategies

• Male-only plasma donor policies have significantly reduced TRALI incidence 2
• Screening donors for leukocyte antibodies, particularly multiparous females 3
• Limiting patient exposure to allogeneic blood products is the most important bedside preventive measure 3