April 22, 2005 — The National Heart, Lung and Blood Institute (NHLBI) developed a working definition of transfusion-related acute lung injury (TRALI) to facilitate diagnosis, reporting, and further research, and published their findings in the April 15 issue of Critical Care Medicine.

"TRALI is now the leading cause of transfusion-associated mortality, even though it is probably still underdiagnosed and underreported," write Pearl Toy, MD, from the University of California–San Francisco, and colleagues from the NHLBI Working Group on TRALI. "Lack of a common definition hampers research and prevents informative comparison of TRALI reports between centers. Current underdiagnosis is due, in part, to excluding patients with other risk factors for acute lung injury (ALI), for example, patients who receive multiple transfusions."

The panel defined TRALI as new ALI occurring during or within six hours posttransfusion, with a clear temporal relationship to the transfusion. This syndrome may range from mild to fatal ALI associated with transfusion of blood and blood components.

The North American-European Consensus Conference defined ALI as acute hypoxemia with PaO ₂/fraction of inspired oxygen [FIO ₂] ratio of 300 mm Hg or less combined with bilateral infiltrates in the absence of left atrial hypertension (ie, circulatory overload). ALI/acute respiratory distress syndrome is a form of permeability pulmonary edema, so the edema fluid to plasma protein ratio is 0.6 or greater.

ALI temporally associated with multiple transfusions can also be TRALI because each unit of blood or blood component can carry one or more of the possible causative agents. These causative agents may include antileukocyte antibody, neutrophil priming agents, biologically active substances, and other agents still to be identified.

To detect TRALI, the panel suggests that pulse oximetry in addition to the usual vital signs monitoring may be reasonable in all transfused patients. They encourage nurses and others who administer transfusions to recognize the signs and symptoms of TRALI in all patients, and physicians to use this definition to diagnose and report cases of TRALI to the local blood bank. Once cases of TRALI are detected, the blood bank should quarantine other units from a suspect donor, investigate implicated donors per local policy, report fatal cases to the Food and Drug Administration, and report nonfatal cases to MedWatch.

Investigators can use this definition to assess incidence, pathophysiology, and preventive strategies. The authors acknowledge that this definition is a good start that will be further refined with additional research.

Limitations of the present definition include identification only of new, severe cases of hypoxemia, and not cases of TRALI in patients who already have ALI, or milder forms of TRALI associated with PaO ₂/FIO ₂ greater than 300 mm Hg or oxygen saturation greater than 90% on room air. A second limitation is that critical care expert assessment of the clinical course is required to diagnose TRALI in a patient with an alternative ALI risk factor, and even experts will consider some cases indeterminate.

Third, other clinical risk factors including major surgery may predispose to TRALI but are not on the list of identified ALI risk factors. Fourth, definitive laboratory tests remain unspecified pending better understanding of etiologies. Finally, the traditional six-hour limit may exclude TRALI cases developing later.

Because patients who have ALI after massive transfusion are included as possible cases of TRALI, the panel addressed whether the multiple donor units transfused within 24 hours should be tested for leukocyte antibody. Because these tests are expensive, the panel concluded that testing should be limited to the units transfused within six hours of development of TRALI.

"As greater understanding is gained into the epidemiology and mechanisms, the definition will change as well," the panel concludes.

Crit Care Med. 2005;33:721-726