Clinical Imaging 37 (2013) 1020–1023 

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: Received 12 July 2012 Received in revised form 19 May 2013 Accepted 25 June 
2013 
Keywords: Acute lung injury Transfusion Computed tomography 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). 
Objective:  The  purpose  of  this  article  is  to  describe  the  clinical  symptoms  and  illustrate  the  radiological  manifestations  of 
transfusion-related  acute  lung  injury  (TRALI)  as  the  condition  develops.  We  mention  those  findings  that  aid the discrimination 
from  transfusion-associated  cardiac  overload.  We  will  also  point  some  of  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  established  using  clinical  and  radiological  parameters.  The  diagnosis  warrants  a  high 
index  of suspicion as well as knowledge of its risk factors. There are no specific treatments; the best chance of survival in TRALI 
is with early diagnosis and prevention. 
© 2013 Elsevier Inc. All rights reserved. 
1. Introduction 
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. 
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 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 
0899-7071/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clinimag.2013.06.008 
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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 
1021 C. Carcano et al. / Clinical Imaging 37 (2013) 1020–1023 
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. 
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 
 
clinical  signs  in  patients  presenting  symptoms  suggestive  of  TACO.  In  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]. 
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. 
8. Conclusion 
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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