Elsevier

The Lancet

Volume 382, Issue 9896, 14–20 September 2013, Pages 984-994
The Lancet

Review
Transfusion-related acute lung injury: a clinical review

https://doi.org/10.1016/S0140-6736(12)62197-7Get rights and content

Summary

Three decades ago, transfusion-related acute lung injury (TRALI) was considered a rare complication of transfusion medicine. Nowadays, the US Food and Drug Administration acknowledge the syndrome as the leading cause of transfusion-related mortality. Understanding of the pathogenesis of TRALI has resulted in the design of preventive strategies from a blood-bank perspective. A major breakthrough in efforts to reduce the incidence of TRALI has been to exclude female donors of products with high plasma volume, resulting in a decrease of roughly two-thirds in incidence. However, this strategy has not completely eradicated the complication. In the past few years, research has identified patient-related risk factors for the onset of TRALI, which have empowered physicians to take an individualised approach to patients who need transfusion.

Introduction

Transfusion-related acute lung injury (TRALI), defined as the onset of respiratory distress after blood transfusion, has long been regarded as a rare complication of transfusion medicine.1 However, in the past decade, perspective has changed. Development of an international consensus definition has aided TRALI research, yielding a higher incidence in specific patient populations than previously acknowledged.2, 3 Patients suffering from a clinical disorder such as sepsis are increasingly recognised as being at risk for development of TRALI.4 Thereby, from a diagnosis by exclusion, TRALI has become the leading cause of transfusion-related mortality.2, 3, 5, 6 However, the syndrome is still underdiagnosed and under-reported in some countries.7, 8, 9

Although blood transfusion can be life saving, it can also be a life-threatening intervention. Physicians use blood transfusion on a daily basis. Increased awareness of the risks of this procedure is needed, because management of patient-tailored transfusion could reduce the risk of TRALI. Such an individualised approach is now possible as insight into TRALI risk factors evolves. Furthermore, proper reporting of TRALI could prevent recurrence. In this Review, we discuss the pathogenesis, incidence, risk factors, and clinical picture of TRALI. We also outline existing strategies to mitigate the syndrome, and the remaining clinical challenges ahead.

Section snippets

Possible TRALI and delayed TRALI

TRALI is a clinical diagnosis for which no diagnostic tests are available. The syndrome was initially regarded as the onset of respiratory distress due to antibody-induced non-cardiogenic lung oedema. Absence of an international definition for TRALI previously contributed to underdiagnosis. As such, a consensus panel, and the US National Heart, Lung and Blood Institute Working Group in 2004, formulated a case definition of TRALI based on clinical and radiological parameters.2, 10, 11 The

The two-hit model

A two-hit hypothesis has been proposed for TRALI.20 The first hit is underlying patient factors, resulting in adherence of primed neutrophils to the pulmonary endothelium. The second hit is caused by mediators in the blood transfusion that activate the endothelial cells and pulmonary neutrophils, resulting in capillary leakage and subsequent pulmonary oedema. The second hit can be antibody-mediated or non-antibody-mediated.

Chain of events

Independent of the transfusion factor, activation of pulmonary

Incidence

TRALI incidence is estimated to be between 0·08% and 15% of patients receiving a blood transfusion (table 1). Diversity in clinical symptoms, absence of specific disease markers and diagnostic tests, and the absence of a clear definition could all have contributed to a large variation in estimations of the incidence of TRALI. Differences in study design should likewise be noted. Passive reporting typically yields lower incidences than active surveillance (table 1). The consensus definition in

Clinical presentation

Respiratory disorders, including dyspnoea, tachypnoea and hypoxaemia, are the central clinical symptoms in TRALI. Such problems are a result of increased pulmonary vascular permeability and ensuing lung oedema. However, a wide range of other reactions can take place because of antibody infusion, including rigors, tachycardia, and fever, and hypothermia and hypotension, and rarely hypertension.59, 60 Bilateral interstitial abnormalities should be present on chest radiograph for the definition of

Treatment

No treatment exists for this life-threatening syndrome. Management of TRALI is supportive. Patients need additional oxygen, and mechanical ventilation is unavoidable in 70–90% of cases.34, 54 TRALI is regarded as part of acute lung injury or acute respiratory distress syndrome; therefore, application of restrictive tidal volume ventilation is logical, because this method is beneficial in patients with these disorders.68 Although some case reports describe use of corticosteroids in patients with

Prognosis

TRALI generally has a good prognosis. Mortality is considered to be low at roughly 5–10%.54, 67, 69 However, data for outcome are sparse, and mostly based on small case series. In observational studies, TRALI mortality was higher in critically ill and surgical patients than in transfused controls.9, 18, 19, 56 An association has also been reported between transfusion of red blood cells, plasma, and platelets, and acute lung injury in several other observational studies.70, 71 However, findings

Patient risk factors for onset of TRALI

In the past 5 years, investigators have identified specific risk factors for TRALI in recipients of blood transfusion. 33% of patients on mechanical ventilation developed acute lung injury within 48 h of transfusion in an observational study.55 A retrospective study confirmed that the presence of mechanical ventilation predisposes to development of TRALI (table 2 and figure 4). Because the application of high peak airway pressures increases the risk for TRALI in patients and in experimental

Restrictive transfusion policy

The most effective prevention is a restrictive transfusion strategy. In a randomised clinical trial in critically ill patients, a restrictive transfusion policy for red blood cells was associated with a decrease in incidence of acute lung injury compared with a liberal strategy (7·7% vs 11·4%),74 suggesting that some of these patients might have had TRALI. The restrictive threshold was well tolerated and has greatly helped in guidance of red blood cell transfusion in the intensive-care unit.74

What can the blood service do?

All blood products can induce antibody-mediated TRALI if the antibody is strong enough and the patient has susceptible risk factors, even red blood cells containing 10–20 mL of plasma (figure 4).86 Instead of focusing on the type of blood product, information about which donors have a high incidence of HLA or HNA antibodies is more important. Two groups of high-risk donors could be identified: multiparous donors and donors exposed to blood transfusion. The likelihood of HLA alloimmunisation in

Conclusion

Despite limitations of diagnostic tests, TRALI incidence seems to be high in at-risk patient populations. Therefore, TRALI is an underestimated health-care problem. Preventive measures, such as mainly male donor strategies, have been successful in reducing risk of TRALI. Identification of risk factors further improves the risk–benefit assessment of a blood transfusion. Efforts to further decrease the risk of TRALI needs increased awareness of this syndrome among physicians.

Search strategy and selection criteria

We searched PubMed from 1980 to 2012, with the terms “transfusion related acute lung injury”, “TRALI”, “plasma”, “storage”, “therapy” and “prevention”, and selected citations on the basis of their specific applicability to specialties pertinent to clinical aspects of TRALI. We largely focused on recent publications and those that have provided pivotal insights into TRALI.

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