What is the relationship between Transfusion-Related Acute Lung Injury (TRALI) and blood transfusion?

From the Guidelines

Transfusion-related acute lung injury (TRALI) is a serious complication that can occur within 6 hours of blood product transfusion, and management primarily involves supportive care, including supplemental oxygen, mechanical ventilation if needed, and discontinuation of the transfusion immediately if TRALI is suspected, as recommended by the most recent guidelines 1. The pathophysiology of TRALI involves neutrophil activation and pulmonary endothelial damage caused by donor antibodies against recipient leukocytes or by bioactive substances in stored blood products. Prevention is key, which includes using leukoreduced blood products, implementing male-only plasma donation policies, and screening donors for HLA antibodies. Some key points to consider in the management of TRALI include:

• Maintaining a low threshold for suspecting TRALI in patients who develop acute respiratory distress during or shortly after transfusion, characterized by hypoxemia, bilateral pulmonary infiltrates, and no evidence of circulatory overload 1.
• Using washed blood products or products from male donors may reduce the risk of TRALI in patients who have previously experienced TRALI 1.
• Most patients recover within 48-96 hours with appropriate supportive care, though mortality rates of 5-10% have been reported. It is essential to note that the decision to transfuse red blood cells should be made based on individual patient needs, and clinicians should weigh the benefits and risks of transfusion, including the risk of TRALI, as outlined in the guidelines 1.

From the Research

Definition and Classification of Acute Lung Injury

• Acute lung injury (ALI) is characterized by acute respiratory insufficiency with tachypnea, cyanosis refractory to oxygen, decreased lung compliance, and diffuse alveolar infiltrates on chest X-ray 2
• The 1994 American-European Consensus Conference defined "acute respiratory distress syndrome, ARDS" by acute onset after a known trigger, severe hypoxemia defined by PaO2/FiO2</=200 mm Hg, bilateral infiltrates on chest X-ray, and absence of cardiogenic edema 2
• Berlin Classification in 2012 defined three categories of ARDS according to hypoxemia (mild, moderate, and severe), and the term "acute lung injury" was assigned for general description or for animal models 2

Transfusion-Related Acute Lung Injury (TRALI)

• TRALI is a serious clinical syndrome associated with the transfusion of plasma-containing blood components 3
• TRALI typically presents as shortness of breath, hypoxemia, hypotension, fever and noncardiogeneic pulmonary edema, all occurring during or within 6 h after transfusion 3
• The mechanism of TRALI has not been fully elucidated, but it has been associated with human leukocyte antigen antibodies (class I, class II or neutrophil alloantigens) and with biologically active mediators in stored cellular blood components 3, 4
• Platelets may be involved in the pathogenesis of TRALI because of their secretory potential and capacity to interact with other immune cells 4

Pathogenesis and Prevention of TRALI

• The pathogenesis of TRALI is thought to involve two steps: a priming step and a second step in which anti-HLA or anti-HNA antibodies or biologically active lipids stress leukocytes and inflame lung epithelia 4
• There is no drug-based prophylaxis, but transfusion strategies are used to mitigate the risk of TRALI 4
• Prevention of TRALI can be achieved through manipulation of the donor pool and through clinical strategies directed at reducing transfusion of blood products, including evidence-based lower transfusion thresholds 5

Role of Platelets in Acute Lung Injury

• The interplay between platelets, leukocytes, and endothelial cells is critical in the pathogenesis of ALI 6
• Key molecules involved in this interaction include P-selectin and the eicosanoid thromboxane A2 (TXA2), suggesting potential new targets for pharmacological intervention 6