Clinical Imaging 37 (2013) 1020–1023

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Clinical Imaging
journal homepage: http://www.clinicalimaging.org

Radiographic manifestations of transfusion-related acute lung injury☆

Carolina Carcano a,⁎, Ndubuisi Okafor b, Felipe Martinez a, Jose Ramirez b, Jeffrey Kanne c, Jacobo Kirsch a
a
Radiology Department, Cleveland Clinic Florida, Weston, FL 33331
b
Pulmonary Department, Cleveland Clinic Florida, Weston, FL 33331
c
Radiology Department, University of Wisconsin, Madison, WI 33331

a r t i c l e i n f o a b s t r a c t

Article history: Objective: The purpose of this article is to describe the clinical symptoms and illustrate the radiological
Received 12 July 2012 manifestations of transfusion-related acute lung injury (TRALI) as the condition develops. We mention those
Received in revised form 19 May 2013 findings that aid the discrimination from transfusion-associated cardiac overload. We will also point some of
Accepted 25 June 2013 the characteristics that increase the risk of TRALI. Conclusion: TRALI generally occurs within 1 to 2 h of the
start of a blood transfusion. Though the radiographic features of TRALI are nonspecific, the diagnosis is
Keywords:
established using clinical and radiological parameters. The diagnosis warrants a high index of suspicion as
Acute lung injury
Transfusion
well as knowledge of its risk factors. There are no specific treatments; the best chance of survival in TRALI is
Computed tomography with early diagnosis and prevention.
TRALI © 2013 Elsevier Inc. All rights reserved.

1. Introduction 2. Incidence

The transfusion-related acute lung injury (TRALI) is a potentially
life-threatening complication of blood transfusion [1,2]. TRALI is
reported as the leading cause of transfusion-related mortality in
the United States [3], presumably related to the international
agreement on its definition, which improved its recognition and
increased the number of reported cases [4]. The National Heart,
Lung, and Blood Institute working group and Canadian Consensus
conference guidelines defined TRALI as a “new acute lung injury
(ALI) that occurs during or within 6 hrs after a transfusion of blood
products, with a clear temporal relationship, in patients with or
without risk factors for ALI other than transfusion” [5,6]. For the
diagnosis of this syndrome, the following criteria should be
present: acute onset, normal pulmonary capillary wedge pressure
or lack of clinical evidence of left atrial hypertension, bilateral
opacities on chest radiograph, and hypoxia [6]. Still, the condition
is thought to be clinically underdiagnosed given that the critically
ill patients often have hypoxia due to pneumonia, sepsis, and
major surgery [4].
We will review the clinical manifestations of TRALI as well as
radiologic findings as the condition develops. An overview of the
characteristics of transfusion-associated cardiac overload (TACO) will
also be discussed given the importance of this alternative condition
within the differential diagnosis of TRALI.
☆ Authors have no financial support and no conflict of interest.
⁎ Corresponding author. Cleveland Clinic Florida, Weston, FL 33331. Tel.: +1 954 689
5123; fax: +1 954 689 5115.
E-mail address: carcanc@ccf.org (C. Carcano).
The first noncardiogenic pulmonary edema termed “transfusion-
related acute lung injury” was presented by Popovsky et al. in 1983
[7–9], although a case report linking symptoms of ALI, transfusion,
and leukoagglutinins was described by Brittingham 25 years before
that [7,10].
According to the records of the Food and Drug administration, 43%
of the fatalities related to blood transfusion in 2011 were caused by
TRALI [11]. The incidence ranges from 0.002% to 1.12% per product
transfused and from 0.08% to 8% per patient transfused [9,12].
According to the US Department of Health, there is an estimated
occurrence of TRALI in 1100 to 10,000 cases of the total of 14.6 million
transfusions done per year in the United States [11]. However, during
the past 7 years, since the standardized definition was developed by
the consensus, there has been an overall decrease in the number of
TRALI fatalities reported [7]. Hemovigilance studies showed that
fresh-frozen plasma products from female donors, especially multip-
arous women, were involved in the majority of the cases of TRALI, as
well as the blood products of a specific patient that had such a
previous reported consequence [13,14].
3. Pathogenesis
The pathogenesis of TRALI has not been fully described, but it is
known to occur with the transfusion of any cell-containing blood
product, cryoprecipitates, intravenous inmunoglobulins, and as little
as 50 ml of plasma-rich blood product [13,15].
Two hypotheses have been formulated related to the lung injury
related to the endothelial damage, capillary leak, and extravasation of
neutrophils occur during TRALI [16,17]. The first hypothesis advocates

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 C. Carcano et al. / Clinical Imaging 37 (2013) 1020–1023 1021

Fig. 1. Case 1: four anteroposterior (AP) radiographs of the chest (A, B, C, and D) of a patient who developed TRALI. (A) Pretransfusion chest radiograph shows clear lungs. (B and C)
Posttransfusion chest radiographs obtained approximately 5 and 40 h after transfusion show developing confluent alveolar opacities with perihilar predominance in the bilateral
mid and lower lung zones. AP radiograph 72 h after transfusion (D) shows partial resolution of lung opacities.

donor antibodies against human leukocyte antigens and human
neutrophil antigens expressed in pulmonary capillaries of the
recipient as the cause of pulmonary damage and capillary leak in
TRALI; however, this association is not very strong [6]. A second
hypothesis implicates a “two-hit” model. The patient has an
inflammatory underlying condition, such as sepsis or recent surgery,
that causes sequestration of neutrophils in the pulmonary compart-
ment. The transfusion of blood products, which include antibodies or
bioactive lipids that accumulated during blood storage, stimulates
those neutrophils to release proteases [4,16,17].
4. Clinical manifestations
The clinical manifestations of TRALI are dyspnea, cyanosis, fever,
tachycardia, hypoxia, hypotension, or less frequently hypertension
[1]. These symptoms may present insidiously, as soon as 1 to 2 h in
90% of the cases, and can lead to the use of life-supporting techniques
such as mechanical ventilation [6].
5. Radiographic manifestations
Chest radiograph is a routine exam for intensive care unit (ICU)
patients. The radiographic features of TRALI are nonspecific. Habitu-
ally, the radiographic findings are worse than the physical exam
findings [10].
An initial chest radiograph shows the combination of interstitial
opacities and diffuse lung haziness, which obscures the pulmonary
vasculature. Septal lines and pleural effusions occasionally develop.
Findings simulate pulmonary edema; the degree of consolidation seen
is related to the extent of alveolar epithelial injury and leakage of fluid
with high protein content into the alveolar spaces [2,12].
The patchy opacities evolve into widespread bilateral alveolar and
interstitial opacities over a short period of time [13]. These findings
are usually indistinguishable from those of hydrostatic pulmonary
edema [10,18]. The lung opacities usually clear within 96 h in 80% of
patients diagnosed with TRALI, as represented in Case 1 (Fig. 1) [19].
Chest computed tomography (CT) evaluation can be helpful in
further assessment of the findings depicted on chest radiograph.
Parenchymal consolidation and air bronchograms, with or without
ground-glass-appearing opacities, are seen in heterogeneous distri-
bution. These findings can be seen in coexistence with normally
aerated lung (as illustrated in Cases 2 and 3 [Figs. 2 and 3]) [12].
6. TRALI versus TACO
According to a Food and Drug Administration report, TACO is the
second most common cause of transfusion-related fatalities (10%
versus 65% associated to TRALI) [3].
Reviewing the patient’s medical history plays an important role in
the differential diagnosis of TRALI and TACO. In patients without
history of heart disease, with ALI risk factors, and negative or neutral
fluid balance, dyspnea would make TRALI more likely than TACO.
Conversely, the evidence of an S3 and elevated jugular venous
pressure would favor TACO.
The profile of the patient at risk for TACO is 3 years or younger, or
older than 60 years [20]. Echocardiography and B-type natriuretic
peptide (BNP) measurements can aid the diagnosis [16]. Indeed, BNP
was found to have significant predictive power independent of other
1022 C. Carcano et al. / Clinical Imaging 37 (2013) 1020–1023

Fig. 2. Case 2: patient with known AML who developed shortness of breath shortly after transfusion. (A) AP radiograph shows clear lungs. Axial (B and C) and coronal reformatted
(D) images of a chest CT scan: lung windows show confluent ground-glass and patchy nodular opacities in the bilateral lungs with somewhat dependent predominance. No
associated septal thickening. Axial image of a chest CT scan: soft tissue window (E) shows small bilateral pleural effusions and mild soft tissue edema.

clinical signs in patients presenting symptoms suggestive of TACO. In 8. Conclusion

the imaging study, identifying vascular congestion and pleural
effusions favors TACO [8].
7. Management and prognosis
Management of TRALI is generally supportive, with most
patients requiring supplementary oxygen. Diuretics, as used for
cardiogenic pulmonary edema, may worsen the condition in a
patient with transfusion-related edema. Corticosteroids have been
used, but there are not adequate studies for or against the use of
such therapy [13].
The mortality rate of TRALI has been reported to range from 6%
to 10% up to 40% in cases that met all of the criteria of the
Consensus Panel. Even though the mortality is still lower than that
of ALI in general (32%), there is no apparent late occurrence of
fibrosis or other structural damage to the lung parenchyma as a
result of TRALI [12].
TRALI is the leading cause of transfusion-related mortality and
occurs early after the beginning of a blood transfusion. With the chest
radiograph being a frequently used tool in patients with acute
respiratory distress in the ICU, the awareness of this entity by the
radiologist is crucial as initial diagnosis depends on a high degree of
suspicion.
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Fig. 3. Case 3: frontal chest radiograph (A) shows multifocal air space opacities in the
bilateral lungs with somewhat perihilar predominance. No significant enlargement of
the cardiac silhouette. Axial images of the chest CT scan: lung windows (B and C) show
confluent alveolar and ground-glass opacities in the bilateral lungs with perihilar
predominance associated to smooth septal thickening. Please note absence of pleural
effusions and normal-sized heart.