BRIEF REPORT

Transfusion-Related Acute Lung Injury

Pearl Toy,

MD*,

and Ognjen Gajic,

MD

*Department of Laboratory Medicine, University of California San Francisco, San Francisco, California; and Division of
Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota

Transfusion-related acute lung injury (TRALI) is the

leading cause of transfusion-related mortality. It is
characterized by injury to the alveolar-capillary membrane precipitated by transfusion factors, antibodies,
and/or inflammatory mediators, in a susceptible host.
In the absence of a specific test, TRALI is defined clinically as a syndrome of acute lung injury that develops
during or within 6 h of transfusion. The absence of left

hat do you think of when you encounter oxygen desaturation in a patient being transfused? Hydrostatic pulmonary edema from
fluid overload may be the most likely cause, especially
in a patient with underlying heart disease. However,
you should also consider permeability pulmonary
edema caused by transfusion-related acute lung injury
(TRALI).
TRALI is now the number one cause of transfusionrelated death, according to the Food and Drug Administration report at the TRALI Conference in Toronto on April 1, 2004. The incidence reported in 1985
was 1 in 5000 U transfused at the Mayo Clinic (1).
Although the current incidence is unknown, the syndrome is thought to be severely under-recognized and
under-reported because of a lack of sensitive and specific diagnostic criteria and poor awareness of the
syndrome outside blood banks. All blood products
have been associated with TRALI, including whole
blood, packed red cells, platelet products, fresh frozen
plasma, and rarely, cryoprecipitate, IV immunoglobulin, and stem cell preparations (2).

atrial hypertension and large protein content of edema

fluid may help differentiate TRALI from hydrostatic
pulmonary edema. The treatment is supportive. The
blood bank needs to be notified promptly so that an
appropriate workup and prevention are initiated in a
timely manner.
(Anesth Analg 2004;99:16234)

(WBCs) which react with and agglutinate patient

WBCs if the patient has the corresponding antigen(s).
These agglutinates lodge in the pulmonary capillary
bed, fix complement, and injure the capillaries, causing capillary leak. WBC antibodies may be directed to
human leukocyte antigen (HLA) class I or II antigens,
or to granulocyte-specific antigens.
Recently, another hypothesis has been developed
(3), proposing a causative role for inflammatory mediators in primed or susceptible patients (two insult
hypothesis). According to this hypothesis, the first
insult is the patients underlying condition (e.g., sepsis, surgery) that primes circulating neutrophils, sequestering them in the lungs. These primed neutrophils
become activated and injure pulmonary capillaries if
exposed to a second insult such as cytokines or lipids,
which accumulate in the plasma of stored red blood cells
and platelets. It is important to realize that the two
hypotheses are not mutually exclusive, and clinical
TRALI may be a common end result of various etiologic
factors. Furthermore, multiple insults (underlying sepsis,
mechanical ventilation, transfusion factors) frequently
coexist and may be required for the development of
acute lung injury (ALI).

Etiology
The cause of TRALI is unclear, and two hypotheses
have been proposed. One is that transfusion of donor
plasma contains antibodies to white blood cells
Accepted for publication June 21, 2004.
Address correspondence and reprint requests to Pearl Toy, MD,
Box 0100, University of California San Francisco, San Francisco, CA
94143-0100. Address e-mail to pearl.toy@clinlab.ucsfmedctr.org.
DOI: 10.1213/01.ANE.0000138033.24633.4E
2004 by the International Anesthesia Research Society
0003-2999/04

Diagnosis
The diagnosis is a clinical one, and there is no single
test for TRALI. TRALI is clinically defined as a new
onset ALI that develops during or within 6 h of transfusion. ALI was defined by the 1994 North American
European Consensus Conference (4) as acute onset of
bilateral infiltrates and hypoxemia in the absence of
increased left atrial pressure. Hypoxemia was defined
Anesth Analg 2004;99:16234

1623

1624

BRIEF REPORT

as a Pao2/Fio2 ratio of 300 mm Hg. Evidence of

increased left atrial pressure includes pulmonary capillary wedge pressure 18 mm Hg or clinical evidence
of left atrial hypertension, including signs of fluid
overload, especially in a patient with underlying congestive heart failure. The presence of left atrial hypertension suggests hydrostatic pulmonary edema as a
cause of acute hypoxemia and bilateral radiographic
infiltrates. It is important to realize that ALI and hydrostatic pulmonary edema may coexist, and the presence
of left atrial hypertension does not necessarily exclude a
TRALI reaction. If undiluted edema fluid is obtained at
the time of endotracheal intubation, the edema fluid to
plasma protein ratio can be determined. A ratio of 0.6
suggests permeability (ALI) rather than hydrostatic pulmonary edema (5). Other signs and symptoms of TRALI
include dyspnea, frothy edema fluid, fever, hypertension
or hypotension (1).
In the absence of other risk factors for acute respiratory distress syndrome (ARDS), e.g., sepsis or gastric aspiration, any new ALI temporally associated
with transfusion is TRALI. Even in the presence of
ARDS risk factor(s), TRALI may still be a significant
contributing factor. Alternatively, such new ALI could
be attibuted to the ARDS risk factor alone, and the
transfusion could have been coincidental and mechanistically unrelated.

Laboratory Findings
Laboratory findings for TRALI are inconsistent and
include acute transient neutropenia (6), matching leukocyte antigen-antibody in the donor-recipient, donor
antibody that activates recipient monocytes (7), and
increased neutrophil priming activity in the transfused unit(s) (3). The blood bank will determine the
appropriateness and feasibility of such laboratory
tests on donor and recipient blood.

Management
Acute management is summarized in Table 1. Units of
blood from donors other than that of the implicated
unit(s) can be transfused without special requirements.
The only caveat is to inform the blood bank that TRALI
is being considered and not to send units from the same
donor, in the unlikely event that such units are in the
blood bank. Management is supportive, which is the
same as management of any patient with permeability
pulmonary edema, and often includes ventilatory support. Lung protective (small tidal volume) ventilatory
strategies should be used. Unless there is concomitant
fluid overload, diuretics are not beneficial.
Suspected TRALI reactions should be reported to
the blood bank and a transfusion reaction workup
initiated. In addition to a posttransfusion patient

ANESTH ANALG
2004;99:16234

Table 1. Immediate Actions When Considering the

Diagnosis of Transfusion-Related Acute Lung Injury
1. Stop the transfusion immediately.
2. Support the patient.
3. If the patient is intubated, obtain undiluted edema fluid
as soon as possible (preferably within 15 min), and
simultaneous plasma for determination of total protein
concentrations.
4. Obtain a complete blood count with differential and
chest radiograph.
5. Notify the blood bank of possible transfusion-related
acute lung injury, request a different unit, and
quarantine other units from the same donor.
6. Follow institutional policies for a transfusion reaction
workup, and send to blood bank:
A patient blood specimen
Bags from units of blood transfused in the last 6 h
A copy of transfusion record forms and anesthesia
record
Indicate the last unit transfused if possible
Results of the patients human leukocyte antigen type
if available

blood specimen, bags from units of blood transfused

in the last 6 h should be returned so that donor plasma
can be tested without recall of the blood donor. A copy
of transfusion record forms and anesthesia record will
allow determination of the sequence and timing of
transfused units. Results of the patients HLA type, if
available, are important to determine whether the donor(s) has corresponding HLA antibodies.
Most patients recover within 24 48 h with supportive care. Mortality has been reported to be 11% (1) to
45% (8). Fatal cases related to transfusion must be
reported by the blood bank to the Food and Drug
Administration within 72 h. Nonfatal cases of TRALI
should be reported by the blood bank to MedWatch.

References
1. Popovsky MA, Moore SB. Diagnostic and pathogenetic considerations in transfusion-related acute lung injury. Transfusion
1985;25:5737.
2. Webert KE, Blajchman MA. Transfusion-related acute lung injury. Transfus Med Rev 2003;17:252 62.
3. Silliman CC, Boshkov LK, Mehdizadehkashi Z, et al.
Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. Blood 2003;101:454 62.
4. Bernard GR, Artigas A, Brigham KL, et al. The AmericanEuropean Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J
Respir Crit Care Med 1994;149:818 24.
5. Fein A, Grossman RF, Jones JG, et al. The value of edema fluid
protein measurement in patients with pulmonary edema. Am J
Med 1979;67:32 8.
6. Yomtovian R, Kline W, Press C, et al. Severe pulmonary hypersensitivity associated with passive transfusion of a neutrophilspecific antibody. Lancet 1984;1:244 6.
7. Kopko PM, Paglieroni TG, Popovsky MA, et al. TRALI: correlation of antigen-antibody and monocyte activation in donorrecipient pairs. Transfusion 2003;43:177 84.
8. Wallis JP, Lubenko A, Wells AW, Chapman CE. Single hospital
experience of TRALI. Transfusion 2003;43:10539.