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.
ReviewTransfusion-related acute lung injury: a clinical review
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
References (100)
- et al.
Proceedings of a consensus conference: towards an understanding of TRALI
Transfus Med Rev
(2005) - et al.
Fatalities caused by TRALI
Transfus Med Rev
(2004) - et al.
Serious hazards of transfusion: a decade of hemovigilance in the UK
Transfus Med Rev
(2006) - et al.
Transfusion related acute lung injury: incidence and risk factors
Blood
(2012) - et al.
The incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: a prospective nested case-control study
Blood
(2011) - et al.
Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors
Blood
(2003) - et al.
Interleukin-8-induced priming of neutrophil oxidative burst requires sequential recruitment of NADPH oxidase components into lipid rafts
J Biol Chem
(2005) - et al.
Leukocyte-endothelial adhesion molecules
Blood
(1994) - et al.
Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice
Blood
(2012) - et al.
Severe pulmonary hypersensitivity associated with passive transfusion of a neutrophil-specific antibody
Lancet
(1984)