Transfusion-Related Acute Lung Injury

Incidence

The incidence of transfusion-related acute lung injury (TRALI) and deaths due to TRALI has decreased substantially over the past decade, as TRALI mitigation strategies have been implemented. In 2006, 35 TRALI-related fatalities were reported to the FDA. These accounted for more than 50% of all transfusion-related fatalities, with 60% of the cases being attributed to plasma products. In contrast, only 12 TRALI fatalities that met definite or probable criteria were reported to the FDA in 2015, comprising 29% of all transfusion-related fatalities. The current incidence of nonfatal TRALI cases is estimated by National Blood Collection and Utilization Surveys to be 1 per 60,000 blood components transfused.

Clinical Manifestations

Typically occurring during or soon after an allogeneic transfusion, signs and symptoms of TRALI include the acute onset of respiratory distress with hypoxemia, dyspnea, and tachypnea; these symptoms may be accompanied by fever, tachycardia, and/or hypotension. Physical examination may reveal rales and diminished breath sounds, without other evidence of fluid overload.

Pathophysiology

The end result of TRALI is an increased permeability of the pulmonary microcirculation, such that high protein fluid enters the interstitium and alveolar air spaces. Both immunologic and non-immunologic mechanisms likely play a role, with two “hits” being necessary to induce TRALI. The first “hit” is related to the patient’s underlying illness status, and the second “hit” involves neutrophil activation induced by transfusion. The majority of cases are immunologic. Some recipient risk factors include recent surgery, active infection, chronic alcohol abuse, shock, higher peak airway pressure while being ventilated, current smoking, and a positive fluid balance.

The primary proposed immunologic mechanism is that human leukocyte antigen (HLA) or human neutrophil antigen (HNA) antibodies in donor plasma react with antigens on recipient leukocytes, which may need to be primed by a coexisting process. This ultimately leads to lung injury, with fluid accumulation in the alveoli. It is also possible that immune complexes of antibody and soluble HNA or HLA may be recognized by neutrophil Fc receptors, that antibodies may induce monocytes or platelets to secrete inflammatory mediators, which then activate neutrophils, or that antibodies may be directed against HLAs on recipient pulmonary interstitial cells.

In some TRALI cases, donor HLA or HNA alloantibodies are not detected; this may be secondary to assay limitations or to a non-immunologic mechanism of TRALI. Non-immunologic mechanisms may include co-transfusion of elements that accumulate during blood storage, including biologically active lipids and/or cytokines.