Transfusion-related Acute Lung Injury

Until recently, TRALI was the most frequent cause of transfusion-related death in the United States (in 2016, Transfusion-associated Circulatory Overload, or “TACO”, overtook TRALI as the most frequent cause). TRALI is defined, according to a National Heart, Lung, and Blood Institute (NHLBI) consensus conference, as acute lung injury (ALI) occurring during or within six hours of transfusion, without other reasons for pulmonary edema. Functionally, that means that TRALI is a clinical diagnosis defined as the combination of: 

• No evidence of acute lung injury before transfusion
• Onset within 6 hours after the transfusion is over
• Hypoxemia (either O2 saturation <90% on room air or PaO2/FiO2 < 200 mm Hg)
• Bilateral chest x-ray infiltrates
• No evidence of circulatory overload

Source: National Healthcare Safety Network Biovigilance Component Hemovigilance Module

TRALI happens by one of two main mechanisms, and possibly a combination of the two. TRALI was first thought to be caused by transfused donor antibodies against either recipient HLA antigens or neutrophil antigens. Such antibodies activate recipient neutrophils, leading them to secrete toxic substances and damage the lining cells (endothelial cells) in pulmonary capillaries, with subsequent pulmonary edema (this mechanism was described initially by Drs. Popovski and Moore at Mayo Clinic). The second mechanism, known as the “two-hit model,” (supported through the work of Dr. Chris Silliman in Denver) requires that a patient’s neutrophils first be sensitized (“primed”) through a significant event, such as massive transfusion, major surgery, or sepsis. A subsequent transfusion of stored blood, which may contain either antibodies (as in the first mechanism) and/or metabolic byproducts of storage (“biologic response modifiers”) induces similar neutrophil activation and pulmonary capillary damage.

Most patients with TRALI recover fairly promptly over the span of several days with respiratory support, but the mortality rate is approximately 10-15%. U.S. blood suppliers and transfusion services are required by AABB to take steps to reduce the incidence of TRALI. Those steps have included the use of predominantly male plasma since the mid-2000s, but as of October 2016, all U.S. plasma and platelet products must come from one of three categories of donor:

• Males
• Females who have never been pregnant (or at least, have never delivered a baby)
• Females who have been pregnant but have been tested and are negative for anti-HLA antibodies

For more on TRALI, especially prevention efforts, please listen to Episode 069CE of the Blood Bank Guy Essentials Podcast.

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