Treatment and Clinical Course - Transfusion-Related Acute Lung Injury (TRALI)
By Tanya Petraszko, MD FRCPC and Heather Hume, MD FRCPC
Treatment of TRALI is supportive. Mild forms of TRALI may respond to supplemental oxygen therapy. Severe forms may require mechanical ventilation and ICU support. As with ARDS there is no role for diuretics or corticosteroids. The majority of patients recover within 72 to 96 hours and subsequently recover to their baseline pulmonary function without apparent sequelae. However, some patients are slower to recover and may remain hypoxic with persistent pulmonary infiltrates up to seven days. As stated above, approximately 5 to 10% of cases are fatal in spite of aggressive supportive care.
Differential Diagnosis
The differential diagnosis of acute lung injury after transfusion includes transfusion-associated circulatory overload (TACO), cardiogenic edema, allergic and anaphylactic transfusion reactions, and bacteremia/sepsis due to transfusion of bacterially contaminated blood products.
TRALI may be distinguished from TACO and cardiogenic pulmonary edema by the absence of signs of circulatory overload such as a normal central venous pressure (CVP) and normal pulmonary capillary wedge pressure (PCWP). Clinical response to diuretics also suggests a diagnosis of TACO rather than TRALI. Allergic and anaphylactic transfusion reactions may be manifest as hypotension and respiratory distress but are marked by laryngeal edema or bronchospasm with wheezing and a normal CXR. Transfusion transmitted bacteremia my present with fever, hypotension, and culminate in severe sepsis with associated acute lung injury which may be difficult to distinguish from TRALI. The presence of positive blood cultures is a useful delineating finding.
Pathophysiology
The hallmark of acute lung injury (ALI) is that of increased pulmonary microvascular permeability with increased protein in the edema fluid. This is true regardless of the cause of the ALI.
It is hypothesized that TRALI may be precipitated by the infusion of donor antibodies directed against recipient leukocytes. The infusion of donor anti-HLA (human leukocyte antigens) or anti-HNA (human neutrophil antigens) antibodies is thought to directly cause complement activation, resulting in the influx of neutrophils into the lung, followed by neutrophil activation and release of cytotoxic agents, with subsequent endothelial damage and capillary leak. Donor derived antibodies to HLA class I antigens and neutrophils have been demonstrated in up to 89% of TRALI cases examined in the literature.
An alternate hypothesis argues that TRALI is the result of at least two independent clinical events: the first is related to the clinical condition of the patient (infection, cytokine administration, recent surgery, or massive transfusion) that causes activation of the pulmonary endothelium. This then leads to the sequestration of primed neutrophils to the activated pulmonary endothelium. The second event is the infusion of donor derived anti-HLA or anti-HNA antibodies directed against antigens on the neutrophil surface and/or biological response modifiers (e.g., lipids) in the stored blood component that activate these adherent, functionally hyperactive neutrophils, causing neutrophil-mediated endothelial damage and capillary leak. Many studies in the literature support this hypothesis which may explain how some TRALI reactions occur in the absence of donor HLA/HNA antibodies, or why TRALI reactions do not occur in all recipients of blood components from donors who are known to have these antibodies.
Yet a third hypothesis suggests that high levels of donor derived vascular endothelial growth factor (VEGF) or antibodies to class II HLA antigens residing on pulmonary vascular endothelium may directly cause endothelial shape change and fenestration. This theory purports to explain the syndrome in neutropenic patients.