Proceedings of a Consensus Conference: Towards an Understanding of TRALI

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Transfusion-related acute lung injury is a relatively uncommon transfusion-associated adverse effect occurring during or soon after an allogeneic blood transfusion. Transfusion-related acute lung injury is a complex syndrome that has many manifestations and has only recently been identified to be an important cause of transfusion-associated morbidity and mortality. But despite its increasing recognition, much about the pathogenesis, treatment, and prevention is poorly understood and often controversial. The purpose of this consensus conference was to bring together international experts in an effort to try to standardize a case definition, which could be used to enhance future understanding of transfusion-related acute lung injury including its epidemiology, pathogenesis, management, prevention, and research. These proceedings are being provided with a view to making available to the transfusion medicine community the considerable amount of important information presented at this consensus conference by the invited international panel of experts.

Section snippets

Introduction to the Consensus Conference

Presented by Graham Sher, MB, BCh, PhD

Canadian Blood Services, Ottawa, Ontario, Canada

Transfusion-related acute lung injury is an uncommon complication of allogeneic blood transfusion, manifested typically by shortness of breath, fever, and hypotension. The TRALI syndrome has been increasingly recognized as an important cause of transfusion-related morbidity and mortality and is considered to be the second or third leading cause of death related to transfusion. It is a complex clinical

TRALI: Background

Presented by Mark A. Popovsky, MD, Haemonetics Corporation, Braintree, Mass

The lung has not traditionally been viewed as a common target of injury after blood transfusion. However, pulmonary complications do occur and include anaphylactic and allergic reactions, circulatory overload, hemolytic transfusion reactions, and bacterial contamination. Transfusion-related acute lung injury appears to be first described by Popovksy et al1 in 1983 and again in 1985.2 However, the syndrome was likely

ARDS—What is it?

Presented by Michelle Ng Gong, MD, MS, Massachusetts General Hospital, Boston, Mass

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) was first described by Ashbaugh and colleagues5 in 1967. They described a series of 12 patients with similar presentations consisting of acute respiratory distress, cyanosis, decreased lung compliance, and bilateral alveolar infiltrates on the chest radiograph. All patients required intubation and ventilation with positive end-expiratory pressure

TRALI: Just ARDS by Another Name?

Presented by Paul C. Hébert, MD, FRCP(C), Ottawa Hospital, General Campus, Ottawa, Ontario, Canada

Illustrative Case Reports

Presented by Kathryn E. Webert, MD, FRCP(C), Canadian Blood Services, Hamilton Centre, Hamilton, Ontario, Canada

Various actual case reports were presented each of which illustrated difficult questions or unresolved issues about TRALI.

Consensus Definition of TRALI Proposed by the TRALI Working Group Convened by the NHLBI

Presented by Pearl Toy, MD, University of California, San Francisco, Calif

Canadian TRALI Experience

Presented by Gilles Delage, MD, MSc, Héma-Québec, Ville St Laurent, Quebec; Heather Hume, MD, FRCP(C), Canadian Blood Services, Ottawa, Ontario; and John Freedman, MD, St Michael's Hospital and Canadian Blood Services, Toronto, Ontario, Canada

Trali Fatalities Reported to the Food and Drug Administration

Presented by Leslie Holness, MD, US Food and Drug Administration, Rockville, Md

The Antibody Hypothesis of TRALI

Presented by Patricia Kopko, MD, Blood Source-Sacramento, Sacramento, Calif

Transfusion-related acute lung injury was first recognized as a discrete and clinical entity by Popovsky and Moore2 in a series of 36 cases from the Mayo Clinic in 1985. Laboratory investigation of these cases identified donor granulocyte antibodies in 89% and lymphocytotoxic antibodies in 72% of cases; HLA class I–specific antibodies were found in 59% of cases tested. Subsequently, in addition to antibodies in donor

An In Vivo Model of TRALI

Presented by Brian Susskind, PhD, Hoxworth Blood Centre, Cincinnati, Ohio

Studies to investigate the pathophysiology of TRALI have been hampered by the lack of an in vivo animal model. Because (a) antileukocyte antibodies may activate recipient cells and induce mediators eliciting the clinical manifestations of TRALI, and because (b) it has been suggested that TRALI may be induced by the transfusion of aged blood containing high concentrations of PAF, even when the transfused blood lacks

Non–Antibody-Mediated TRALI

Presented by Chris Silliman, MD, PhD, Bonfils Blood Centre, Denver, Colo

In addition to the above-described mechanism of cytotoxic antibody-mediated TRALI, Silliman et al28., 29. proposed a 2-event model, based on the pathogenesis of ARDS, to explain the pathophysiology in cases where no antibody is detected. The first event is a predisposing clinical condition of the patient, for example, recent surgery, active infection, or massive transfusion, which induces pulmonary endothelial cell

Clinical Data Supporting the 2-Event Model

Presented by Lynn Boshkov, MD, Oregon Health & Science University, Portland, Ore

A series of 90 reactions in 81 consecutive patients with TRALI at one center over 4 years supported the 2-event model.29 In addition, a nested case control study in 46 patients with TRALI transfused with platelets and 225 randomly selected hospitalized control subjects who received platelet transfusions but did not experience a reaction was described. The frequency of leukocyte antibodies was similar in control

Proposed Patient/Donor Testing

Presented by Daniel R. Ambruso, MD, Bonfils Blood Centre, Denver, Colo

Transfusion-related acute lung injury is an underreported and sometimes severe complication of blood transfusion. Transfusion-related acute lung injury may complicate preexisting lung disease. Testing based on the etiologies described for the disease will not only define the existence of this syndrome in patients suffering from ALI, but will aid in the development of strategies to prevent and treat this complication of

Algorithms for the Investigation of Reports of TRALI in Transfusion Recipients

Presented by Edward Snyder, MD, Yale-New Haven Hospital, New Haven, Conn

Transfusion-related acute lung injury has doubtless been occurring in transfusion recipients for many years but has been largely unrecognized as such because of the lack of appreciation of the clinical syndrome by clinicians and transfusion medicine specialists alike. Now it is recognized that TRALI is not only underreported, but that it presents as a spectrum of transfusion reactions that range from a mild almost

Serious Hazards of Transfusion Scheme Experience and the UK Initiatives on TRALI Prevention and Their Potential Impact

Presented by Lorna Williamson, BSc, MD, FRCP(C), FRCPath, University of Cambridge/National Blood Service, Cambridge, UK

The Serious Hazards of Transfusion Scheme (SHOT) is a UK-wide hemovigilance program, launched in 1996, which receives and collates reports of serious transfusion incidents, makes recommendations to improve transfusion safety, and plays an education role about adverse transfusion events. Reports are confidential, anonymous, and voluntary, although most hospitals now participate

Animal Model of TRALI and the European TRALI Experience

Presented by Jüergen Bux, PhD, Swiss Red Cross Blood Centre of Berne, Berne, Switzerland

Antibody-mediated TRALI is thought to be due to antileukocyte antibodies found in plasma-containing blood components that bind to HLA antigens and human neutrophil alloantigens (HNA) on the surface of recipient neutrophils (Table 10).

The leukocyte antibodies activate and aggregate the neutrophils so that they adhere to the endothelium of the pulmonary capillaries and release toxic mediators, resulting in

Donor Management Issues in TRALI

Presented by Paul Holland, MD, Blood Source-Sacramento, Sacramento, Calif

An important consideration regarding TRALI is donor management. It is essential to balance the need for an adequate blood supply with patient safety.

Current strategies for prevention and management of TRALI are based on the assumption that donor antibodies are the major etiologic factor in this disorder. If other factors relating to either the product or the recipient are also important, strategies for addressing these

Managing Risk in the Face of Uncertainty: How Useful is the Precautionary Principle?

Presented by Kumanan Wilson MD, MSc, FRCP(C), Department of Medicine, University of Toronto, Toronto, Ontario, Canada

The precautionary principle has gained increasing acceptance as a tool for risk management decision making. This principle has recently been applied in transfusion medicine decisions relating to variant Creutzfeldt-Jacob Disease (vCJD) and the safety of the blood supply. Although this approach has many strengths, there are also significant limitations inherent in the application

Open Discussion

Lead by Gilles Delage, MD, Héma-Québec, Montreal, Québec, Canada

Acknowledgments

The authors of these proceedings would like to take this opportunity to thank and acknowledge the significant contributions of the panel of experts, who presented data to the TRALI Consensus Conference, for their cooperation in reviewing the summaries of their presentations for accuracy. We would also like to thank the members of the consensus conference steering committee: Morris A. Blajchman (Chair), Gwen Clark, Gilles Delage, Sunny Dzik, John Freedman, Mindy Goldman, Heather Hume, Harvey

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