Clinical Imaging 37 (2013) 1020–1023

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Clinical Imaging

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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 33331b Pulmonary Department, Cleveland Clinic Florida, Weston, FL 33331c Radiology Department, University of Wisconsin, Madison, WI 33331

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

☆ Authors have no financial support and no conflict o⁎ Corresponding author. Cleveland Clinic Florida, West

5123; fax: +1 954 689 5115.E-mail address: carcanc@ccf.org (C. Carcano).

0899-7071/$ – see front matter © 2013 Elsevier Inc. Alhttp://dx.doi.org/10.1016/j.clinimag.2013.06.008

Article history:

Received 12 July 2012Received in revised form 19 May 2013Accepted 25 June 2013

Keywords:Acute lung injuryTransfusionComputed tomographyTRALI

Objective: The purpose of this article is to describe the clinical symptoms and illustrate the radiologicalmanifestations of transfusion-related acute lung injury (TRALI) as the condition develops. We mention thosefindings that aid the discrimination from transfusion-associated cardiac overload. We will also point some ofthe characteristics that increase the risk of TRALI. Conclusion: TRALI generally occurs within 1 to 2 h of thestart of a blood transfusion. Though the radiographic features of TRALI are nonspecific, the diagnosis isestablished using clinical and radiological parameters. The diagnosis warrants a high index of suspicion aswell as knowledge of its risk factors. There are no specific treatments; the best chance of survival in TRALI iswith early diagnosis and prevention.

© 2013 Elsevier Inc. All rights reserved.

1. Introduction

The transfusion-related acute lung injury (TRALI) is a potentiallylife-threatening complication of blood transfusion [1,2]. TRALI isreported as the leading cause of transfusion-related mortality inthe United States [3], presumably related to the internationalagreement on its definition, which improved its recognition andincreased the number of reported cases [4]. The National Heart,Lung, and Blood Institute working group and Canadian Consensusconference guidelines defined TRALI as a “new acute lung injury(ALI) that occurs during or within 6 hrs after a transfusion of bloodproducts, with a clear temporal relationship, in patients with orwithout risk factors for ALI other than transfusion” [5,6]. For thediagnosis of this syndrome, the following criteria should bepresent: acute onset, normal pulmonary capillary wedge pressureor lack of clinical evidence of left atrial hypertension, bilateralopacities on chest radiograph, and hypoxia [6]. Still, the conditionis thought to be clinically underdiagnosed given that the criticallyill patients often have hypoxia due to pneumonia, sepsis, andmajor surgery [4].

We will review the clinical manifestations of TRALI as well asradiologic findings as the condition develops. An overview of thecharacteristics of transfusion-associated cardiac overload (TACO) willalso be discussed given the importance of this alternative conditionwithin the differential diagnosis of TRALI.

f interest.on, FL 33331. Tel.: +1 954 689

l rights reserved.

2. Incidence

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 beforethat [7,10].

According to the records of the Food and Drug administration, 43%of the fatalities related to blood transfusion in 2011 were caused byTRALI [11]. The incidence ranges from 0.002% to 1.12% per producttransfused and from 0.08% to 8% per patient transfused [9,12].According to the US Department of Health, there is an estimatedoccurrence of TRALI in 1100 to 10,000 cases of the total of 14.6 milliontransfusions done per year in the United States [11]. However, duringthe past 7 years, since the standardized definition was developed bythe consensus, there has been an overall decrease in the number ofTRALI fatalities reported [7]. Hemovigilance studies showed thatfresh-frozen plasma products from female donors, especially multip-arous women, were involved in the majority of the cases of TRALI, aswell as the blood products of a specific patient that had such aprevious reported consequence [13,14].

3. Pathogenesis

The pathogenesis of TRALI has not been fully described, but it isknown to occur with the transfusion of any cell-containing bloodproduct, cryoprecipitates, intravenous inmunoglobulins, and as littleas 50 ml of plasma-rich blood product [13,15].

Two hypotheses have been formulated related to the lung injuryrelated to the endothelial damage, capillary leak, and extravasation ofneutrophils occur during TRALI [16,17]. The first hypothesis advocates

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 bilateralmid and lower lung zones. AP radiograph 72 h after transfusion (D) shows partial resolution of lung opacities.

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

donor antibodies against human leukocyte antigens and humanneutrophil antigens expressed in pulmonary capillaries of therecipient as the cause of pulmonary damage and capillary leak inTRALI; however, this association is not very strong [6]. A secondhypothesis implicates a “two-hit” model. The patient has aninflammatory 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 orbioactive lipids that accumulated during blood storage, stimulatesthose 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 in90% of the cases, and can lead to the use of life-supporting techniquessuch 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 examfindings [10].

An initial chest radiograph shows the combination of interstitialopacities and diffuse lung haziness, which obscures the pulmonaryvasculature. 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 fluidwith high protein content into the alveolar spaces [2,12].

The patchy opacities evolve into widespread bilateral alveolar andinterstitial opacities over a short period of time [13]. These findingsare usually indistinguishable from those of hydrostatic pulmonaryedema [10,18]. The lung opacities usually clear within 96 h in 80% ofpatients diagnosed with TRALI, as represented in Case 1 (Fig. 1) [19].

Chest computed tomography (CT) evaluation can be helpful infurther assessment of the findings depicted on chest radiograph.Parenchymal consolidation and air bronchograms, with or withoutground-glass-appearing opacities, are seen in heterogeneous distri-bution. These findings can be seen in coexistence with normallyaerated 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 thesecond most common cause of transfusion-related fatalities (10%versus 65% associated to TRALI) [3].

Reviewing the patient’s medical history plays an important role inthe differential diagnosis of TRALI and TACO. In patients withouthistory of heart disease, with ALI risk factors, and negative or neutralfluid balance, dyspnea would make TRALI more likely than TACO.Conversely, the evidence of an S3 and elevated jugular venouspressure would favor TACO.

The profile of the patient at risk for TACO is 3 years or younger, orolder than 60 years [20]. Echocardiography and B-type natriureticpeptide (BNP) measurements can aid the diagnosis [16]. Indeed, BNPwas found to have significant predictive power independent of other

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. Noassociated septal thickening. Axial image of a chest CT scan: soft tissue window (E) shows small bilateral pleural effusions and mild soft tissue edema.

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clinical signs in patients presenting symptoms suggestive of TACO. Inthe imaging study, identifying vascular congestion and pleuraleffusions favors TACO [8].

7. Management and prognosis

Management of TRALI is generally supportive, with mostpatients requiring supplementary oxygen. Diuretics, as used forcardiogenic pulmonary edema, may worsen the condition in apatient with transfusion-related edema. Corticosteroids have beenused, but there are not adequate studies for or against the use ofsuch 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 theConsensus Panel. Even though the mortality is still lower than thatof ALI in general (32%), there is no apparent late occurrence offibrosis or other structural damage to the lung parenchyma as aresult of TRALI [12].

8. Conclusion

TRALI is the leading cause of transfusion-related mortality andoccurs early after the beginning of a blood transfusion. With the chestradiograph being a frequently used tool in patients with acuterespiratory distress in the ICU, the awareness of this entity by theradiologist is crucial as initial diagnosis depends on a high degree ofsuspicion.

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Fig. 3. Case 3: frontal chest radiograph (A) shows multifocal air space opacities in thebilateral lungs with somewhat perihilar predominance. No significant enlargement ofthe cardiac silhouette. Axial images of the chest CT scan: lung windows (B and C) showconfluent alveolar and ground-glass opacities in the bilateral lungs with perihilarpredominance associated to smooth septal thickening. Please note absence of pleuraleffusions and normal-sized heart.

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