Transfusion-Related Acute Lung Injury

Etiology

True TRALI should not have any risk factors for acute lung injury according to diagnostic criteria. TRALI is caused by damage to pulmonary vasculature from neutrophil-mediated in forms of human neutrophil antigen (HNA) or human leukocyte antigen (HLA) antibodies in donor blood which bind to antigens of a recipient. Storage of blood products can accumulate proinflammatory mediators that can cause TRALI as well. A two-hit hypothesis applies in this clinical syndrome. Neutrophil sequestration occurs in the pulmonary vasculature, and neutrophils activate to damage the endothelial layer, causing leakage of protein and fluid into alveolar space.[9][10]

Epidemiology

Comorbidities suggest risk factors for having TRALI, mechanical ventilation, sepsis, massive transfusion, coronary artery bypass graft, and end-stage liver disease.[3] Higher TRALI incidence was reported with plasma from female donors because the literature found parous female donors with multiple HLA antibodies.[11] Other literature mentioned female donor plasma has larger quantities of anti-HLA class II and HNA positive antibodies. Blood products that have high plasma contents have been associated with an increased rate of TRALI. Critically ill patients have a higher incidence of TRALI, not only because they receive more blood products, but they also have clinical manifestations that activate neutrophil sequestration before the blood transfusion which places them at a higher risk of acquiring TRALI than the general patient population.

In the US, TRALI has been responsible for at least 30% of transfusion-related deaths. While the mortality rates have dropped over the past decade, continued awareness is key.

Pathophysiology

Due to the two-hit hypothesis, the first hit takes place by priming of neutrophils from who are already ill from shock, sepsis, having organ damage who also had surgery or experienced a great deal of stress from trauma.[12] Increased levels of interleukin-8, interleukin-6, and elastase-alpha 1-antitrypsin complex cause neutrophil recruitment to the pulmonary vasculature.[5] Conformational change in beta-2 integrins allows neutrophil to adhere to pulmonary capillaries.[13][14] The second hit comes from the transfusion itself. Antibodies and bioactive lipids stored in blood products activate neutrophils, resulting in capillary leakage of intracellular content-releasing proteases and elastase from the activation of NADPH which eventually oxidase, causing pulmonary edema. Another hypothesis is called the threshold hypothesis. There is no first hit involved. TRALI can happen in healthy patients who are transfused with plasma that has high amounts of antibodies whose neutrophil has already activated.

Histopathology

Histopathology consists of early acute lung distress syndrome (ARDS), revealing interstitial and intra-alveolar edema and the presence of neutrophils in the interstitial and airway. Lung sections have shown numerous neutrophils in pulmonary capillaries and small pulmonary vessels.[15]

History and Physical

Before a blood transfusion, a complete history and physical exam needs to be done to assess the patient's clinical status. Most likely, the hemoglobin is lower than 7, or they are actively bleeding and need a red blood cell transfusion. Abnormal coagulation studies with consumptive coagulopathy also warrant correction with FFP or cryoprecipitate before any interventions or emergent surgery. Within 6 hours of blood transfusion for acute TRALI or 6 to 72 hours for delayed TRALI, patients can develop body temperature of greater than 100.4 degrees Fahrenheit or 37 degrees Celcius or hypotension along with acute dyspnea requiring more oxygen via nasal cannula, nonbreathable mask or even mechanical ventilation depending on severity.[8][5] Patients might use accessory muscles for respiration and appear to be in acute distress with breathing. Because this is not fluid overload or cardiogenic edema, neck veins are not distended. Auscultation of the lungs reveals rales and sometimes diminished breath sounds due to pulmonary edema. TRALI is almost impossible to distinguish from ARDs based on clinical presentation.

Evaluation

A chest radiograph will show bilateral pulmonary infiltrates. Clinical characteristics of TRALI include acute dyspnea, hypoxemia, fever, hypotension, tachycardia, leukopenia, thrombocytopenia, and normal pulmonary artery occlusion pressure due to noncardiogenic pulmonary edema.[8]

Nearly 30% of patients will have low levels of BNP and transient leucopenia.

Treatment / Management

Immediate management of TRALI is to stop the transfusion and notify the blood bank to screen the donor unit for antileukocyte antibodies, anti-HLA or anti-neutrophil-specific antibodies.[5] Supportive measures must be taken to improve oxygenation. Although there is no specific treatment for TRALI, low tidal volume application is feasible in this case as TRALI's pathophysiology is similar to acute lung distress syndrome (ARDS). Best practice is prevention. In the United Kingdom, the incidence of TRALI was substantially reduced by using plasma from male donors and screening female donors for HLA and HNA antibodies which are strong risk factors.

Once the transfusion is stopped, gradual recovery may take 2-4 days. The chest x-ray will improve within 2-5 days.

Differential Diagnosis

When there is a transfusion reaction with acute dyspnea from respiratory distress, acute pulmonary edema with diffuse bilateral infiltrates in the chest x-ray, transfusion-associated circulatory overload (TACO) is in the differential diagnosis. TACO is also a clinical diagnosis with similar clinical pictures as TRALI. However, there are distinct features that separate two syndromes. TACO can present with fever and hypotension. Even though normal fluid balance does not rule out TACO, it can happen to patients who have high fluid intake before the transfusion. Due to volume overload, patients with TACO can have distended neck veins and already reduced ejection fraction (EF) from heart failure with reduced EF. Pulmonary artery occlusion pressures could be 18 mmHg or greater, secondary to cardiogenic pulmonary edema with elevated brain natriuretic peptide. Because of cardiogenic pulmonary edema, TACO has transudate fluids which are low in plasma proteins.[3]

Prognosis

Despite aggressive support, mortality rates of more than 12% are reported once TRALI is diagnosed. Even those who survive have a slow recovery.