Transfusion medicine handbook

7. Adverse Effects of Transfusion

7.12 Transfusion-related Acute Lung Injury

Transfusion-related acute lung injury (TRALI) is a significant transfusion-related event. Although poorly recognised and undoubtedly underreported, international haemovigilance data indicates that it is one of the most common causes of fatal transfusion reactions.

TRALI is characterised by acute respiratory distress due to non-cardiogenic pulmonary oedema, developing during or within 6 hours of transfusion. Typically, plasma components containing antibodies against the patient's white blood cells are implicated. Transfusion is followed by a (usually) severe reaction with acute respiratory distress, accompanied by chills and/or fever. The chest X-ray shows numerous, mainly perihilar, nodules with infiltration of the lower lung fields without cardiac enlargement or engorgement of the vessels. A transient leucopenia or neutropenia may be seen. The implicated donors are almost always alloimmunised multiparous women. However the number of reactions seen where antibodies are either not identified or cannot be serologically implicated suggests the involvement of other mechanisms and risk factors.

The diagnosis of TRALI is therefore a clinical and radiographic diagnosis and is not dependent on the results of laboratory tests or any proposed pathophysiologic mechanisms. TRALI should be considered a clinical syndrome rather than a disease with a single cause. Treatment usually involves intensive care respiratory support.

Reporting to the NZBS Transfusion Medicine Specialist is essential so that an implicated donor can be retired from further donations.

Testing of donors implicated in TRALI events

One proposed mechanism for TRALI is the interaction between human leucocyte antigen (HLA) or neutrophil-specific (HNA) antibodies of donor origin and the recipient’s white cells. NZBS has developed a standard procedure for investigating TRALI events, including relevant serological testing. The investigation includes testing of the donor(s) and recipient for HLA class I and II antibodies (identifying specificity if detected) and for HNA antibodies. Antibody detection and identification is complemented by HLA typing to confirm presence of the corresponding antigen(s).

TRALI risk reduction

A number of countries, including New Zealand, have introduced a strategy for reducing the frequency of TRALI involving the use of FFP manufactured from plasma collected only from male donors. The use of male-only donors for FFP appears to reduce the incidence of TRALI. In addition, female plateletpheresis donors with a history of pregnancy to > 20 weeks gestation are tested for the presence of HLA antibodies. Where positive, donors are deferred from donating apheresis platelets and whole blood donations are excluded from processing to platelet pools.

The differential diagnosis of TACO and TRALI

Acute respiratory distress during or shortly following transfusion may be due to TACO, TRALI, a severe allergic reaction or the patient’s underlying condition. Unfortunately, many of the early signs and symptoms are not discriminatory and can occur in other types of transfusion reactions. Most FNHTR and allergic reactions can however be readily identified as such.

It is important to distinguish between TACO and TRALI because of the relatively high mortality for TRALI. Invasive measurements such as central venous and pulmonary wedge pressures may be useful (elevated in TACO) but are not consistently diagnostic or readily available, particularly in less severe cases. It has been suggested that measurement of serum B-type natriuretic peptide (BNP) or the accompanying N-terminal fragment (NT-pro BNP) might be useful in the differential diagnosis of TACO. BNP is secreted from the cardiac ventricles as a result of ventricular pressure overload and volume expansion, such as occurs with TACO. Low levels of BNP can help exclude TACO however, whilst high levels may favour TACO they do not necessarily exclude TRALI or allergic reactions, as these can co-exist.