Transfusion Related Acute Lung Injury

Transfusion-related acute lung injury (TRALI) is a rare but devastating complication of blood component therapy. Clinically, these patients present with findings similar to that of adult respiratory distress syndrome, consisting of hypotension, fever, dyspnea, and tachycardia. Noncardiogenic pulmonary edema with diffuse bilateral pulmonary infiltrates on chest radiography is characteristic. The onset typically occurs within 6 hours of transfusion, but most cases present within 1 to 2 hours. Transfusions of all blood products have been associated with the disease.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY

CHARACTERIZATION

INCIDENCE

0.04% and 0.06% per transfusion, or approximately 1 in 2000 transfusions

Transfusion-Related Acute Lung Injury

Report of a Clinical Look-Back Investigation

Patricia M. Kopko, MD; Carol S. Marshall, MD; Malcolm R. MacKenzie, MD; Paul V. Holland, MD; Mark A. Popovsky, MD

JAMA. 2002;287:1968-1971 Abstract quote

Context
Transfusion-related acute lung injury (TRALI) is a syndrome that includes dyspnea, hypotension, bilateral pulmonary edema, and fever. TRALI is the third leading cause of transfusion-related mortality, but it is probably underdiagnosed and underreported.

Objective
To determine if blood products from a frequent plasma donor, whose blood product was implicated in a fatal case of TRALI, caused symptoms of TRALI in other recipients of her plasma.

Design, Setting, and Participants
Retrospective chart review (conducted from November 2000 through April 2001) of 50 patients who received blood components within 2 years (October 1998 through October 2000) from a donor linked to a transfusion-related fatality.

Main Outcome Measure
Occurrence of mild/moderate (dyspnea with fever, chills, hypotension, and/or hypoxemia) or severe (acute pulmonary edema or need for mechanical ventilation) reaction associated with transfusion.

Results
Superimposed illness prevented assessment of TRALI in 14 patients. Of the 36 patient charts that could be reviewed, 7 mild/moderate reactions were reported in 6 patients (16.7%) and 8 severe reactions were reported in 8 patients (22.2%). Of 5 patients who received multiple transfusions from the same donor, 2 experienced 2 reactions: one had 2 mild/moderate reactions and the other had both a mild/moderate and a severe reaction. While 5 of the 7 mild/moderate reactions were reported to the hospital transfusion service, only 2 of the 8 severe reactions were reported. Only 2 reactions (1 mild/moderate and 1 severe) were reported to the regional blood collection facility.

Conclusions
TRALI was frequently underdiagnosed and underreported in recipients of blood products from a donor whose blood products may have caused TRALI in several transfusion recipients. Clinical education and awareness of this often-overlooked diagnosis are imperative for appropriate prevention and treatment.

DISEASE ASSOCIATIONS

CHARACTERIZATION

Transfusion-Related Acute Lung Injury Secondary to Biologically Active Mediators

Susan E. Lenahan, etal.

Arch Pathol Lab Med 2001;125:523�526. Abstract quote

Transfusion-related acute lung injury is seen following the transfusion of blood components. The reported incidence is approximately 1 in 2000 transfusions. Clinically, it is similar to adult respiratory distress syndrome. The pathophysiology is unclear but has been attributed to HLA antibodies, granulocyte antibodies, and more recently to biologically active mediators in stored blood components.

We report a case with laboratory evidence that supports the role of biologically active mediators in the pathogenesis of transfusion-related acute lung injury.

To our knowledge, the case reported here is the first to use lipid extractions of patient samples to determine that lipid-priming activity was present at the time transfusion-related acute lung injury was identified clinically.

PATHOGENESIS

CHARACTERIZATION

Immune complexes

Transfusion 1997;37:719�726.
J Clin Invest 1998;101:1458�1467.

Immune complexes are formed and entering the pulmonary vascular bed stimulate the release of vasoactive substances that cause the leakage of fluid into alveolar spaces, activation of complement, leukostasis, and activation of polymorphonuclear neutrophils

A septic rat model demonstrated the development of acute lung injury following the transfusion of plasma or extracted plasma lipids from stored blood suggesting that biologically active lipids coupled with the underlying disease state set the stage for the development of TRALI

CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Transfusion-related acute lung injury: a case-control pilot study of risk factors. Sanchez R, Bacchetti P, Toy P. Department of Laboratory Medicine, University of California San Francisco, CA 94143, USA.	Am J Clin Pathol. 2007 Jul;128(1):128-34. Abstract quote Transfusion-related acute lung injury (TRALI) is the leading cause of mortality from transfusion therapy. Recipient, donor, and blood product risk factors may have important roles in the occurrence of TRALI. A case-control pilot study of 6 TRALI cases in which HLA-antibody concordance was found and 20 control subjects was conducted to evaluate recipient and donor predictors of TRALI. By using stratified exact logistic regression, characteristics of the recipients, donors, and blood products were analyzed and the results reported as odds ratios. The risk for TRALI was increased per unit of whole blood transfused (odds ratio, 3.0 per unit; P = .0098). A larger prospective case-control study is underway to determine recipient, donor, and blood product risk factors associated with TRALI.
VARIANTS
Transfusion-Related Acute Lung Injury Resulting From Designated Blood Transfusion Between Mother and Child A Report of Two Cases Xu Yang, MD,	Am J Clin Pathol 2004;121:590-592 Abstract quote Transfusion-related acute lung injury (TRALI) is an underdiagnosed serious complication of blood transfusion characterized by the rapid onset of respiratory distress, hypoxia, and noncardiogenic pulmonary edema during or soon after blood transfusion. The presence of anti-HLA and/or antigranulocyte antibodies in the plasma of donors is implicated in the pathogenesis of TRALI. We report 2 cases of TRALI that were caused by designated blood transfusion between mothers and their daughters; one in a 4-month-old girl who received designated packed RBCs donated by her mother and the second in a 78-year-old mother who received blood from her daughter. In both cases, examination of mother's serum revealed panel-reactive cytotoxic HLA antibodies. It is most likely that the mothers were sensitized from earlier pregnancy and produced HLA antibodies against the daughters' paternally derived HLA antigens. Designated blood transfusion between multiparous mothers and children might add an additional transfusion-related risk owing to the higher likelihood of the HLA antibody-antigen specificity between mother and child.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	Most symptoms resolve within 96 hours after ventilatory support
Survival	Mortality rate is reported to be 5% to 10%
Treatment	Transfus Med Rev 1999;13:177�186. Br J Haematol 1999;105:322�329. Generally supportive and similar to that for adult respiratory distress syndrome. Ventilatory and hemodynamic assistance are utilized as required There are no clear indications for the use of corticosteroids, and their use remains controversial in this setting Additional blood component therapy should not be withheld if clear indications for transfusion exist

Transfus Med Rev 1999;13:177�186
Br J Haematol 1999;105:322�329.