Trali Uptodate PDF

7/12/2015 Transfusion-related acute lung injury (TRALI)
http://www.uptodate.com.ezproxy.ugm.ac.id/contents/transfusion-related-acute-lung-injury-trali?topicKey=HEME%2F7926&ela
psedTimeMs=0&source=searc... 1/20
®
®
● (See "Immunologic blood transfusion reactions".) ● (See "Transfusion reactions caused by chemical
and physical agents".) ● (See "Noncardiogenic pulmonary edema".) ●
(See "Acute respiratory distress syndrome: Clinical features and diagnosis in adults".) (See "Acute
respiratory distress syndrome: Epidemiology, pathophysiology, pathology, and etiology in adults".)
Official reprint from UpToDate www.uptodate.com ©2015 UpToDate
Transfusionrelated acute lung injury (TRALI)

Authors
Section Editors
Deputy Editor Steven
Kleinman, MD
Arthur J Silvergleid, MD
Jennifer S Tirnauer, MD
Daryl J Kor, MD
Scott Manaker, MD, PhD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2015. | This topic last updated: Dec 15, 2014.
INTRODUCTION — Transfusionrelated acute lung injury (TRALI) is a rare but potentially fatal
complication of blood product transfusion. TRALI has been defined by both a National Heart, Lung, and
Blood Institute (NHLBI) working group as well as a Canadian Consensus Conference, as new acute lung
injury (ALI)/acute respiratory distress syndrome (ARDS) occurring during or within six hours after blood
product administration (table 1) [1,2]. When a clear temporal relationship to an alternative risk factor for
ALI/ARDS coexists, a formal diagnosis of TRALI cannot be made. In these circumstances, the diagnostic
terminology to be used is "possible TRALI."
Prior to the institution of TRALI risk mitigation strategies, plasma components and apheresis platelet
concentrates conferred the highest risk of TRALI per component. Currently, due to transfusion of a much
larger number of red cell units compared with plasma and platelets, the largest number of TRALIrelated
deaths in the United States and other developed countries occur with red blood cell transfusion [3]. (See
'Prevention' below.)
The epidemiology, pathogenesis, risk factors, clinical features, management, and prevention strategies for
TRALI are presented here. General issues related to blood transfusion, other reactions to transfusion
therapies, and general issues related to acute lung injury are discussed separately.
●
EPIDEMIOLOGY — Historical estimates suggest that TRALI occurs at a rate of approximately 0.04 to
0.1 percent of transfused patients or in approximately 1 in 5000 transfused blood components [47].
However, the true incidence of TRALI is not known, largely due to poor syndrome recognition, the
reliance on passive reporting rather than active surveillance strategies, and the inclusion of cases that did
not meet the NHLBI or Canadian Consensus Conference definitions of TRALI in some reports [3,811].
Additionally, due to the contribution of specific recipient risk factors, TRALI incidence is also likely to
depend on the population of interest. As an example, estimates suggest that the rate of TRALI in critically
ill populations may reach 5 to 8 percent [12,13]. (See 'Recipient risk factors' below.)
Importantly, the incidence of TRALI has decreased dramatically following the institution of TRALI
mitigation strategies for transfused plasma and platelet components that were instituted in the mid to late
2000s. (See 'Prevention' below.)
As an illustration of this, TRALI cases were identified using a prospective systematic method at a rate of
0.0081 percent (ie, 1 in 12,345) in the year 2009 [14,15]. This was substantially lower than the incidence
rate of 0.0257 percent (ie, 1 in 3891) in the year 2006, determined with the same case detection strategies
[14,15]. Even though case surveillance in this study was active and prospective, underreporting still may
have occurred, as has been the case with other published estimates [6].
TRALI is the leading cause of transfusionrelated mortality in the United States [3]. Historical estimates
for TRALI–associated mortality have ranged from 5 to 8 percent [16]. However, evidence from large

hemovigilance networks suggests higher mortality rates in the range of 13 to 21 percent [8,1719]. Not
surprisingly, the mortality rate for TRALI/possible TRALI in critically ill populations appears
substantially higher, in the range of 35 to 58 percent [12,13].
RISK FACTORS — Specific risk factors for TRALI can be divided conceptually into recipient risk
factors and blood component risk factors.
Recipient risk factors — TRALI has been reported to occur in essentially all age groups and equally in
both sexes [2022]. The presence of an underlying condition such as recent surgery, cytokine treatment,
massive blood transfusion, and active infection have been implicated in some, but not all, studies
[4,17,18,21,2328]. The critically ill appear to be at highest risk for TRALI [12,13,29].
Studies evaluating TRALI risk factors are limited by a relatively small number of TRALI cases available
for analysis and the use of varied diagnostic criteria. The following studies are illustrative of the available
data:
A multicenter prospective cohort investigation using active surveillance strategies for TRALI detection
identified recipient risk factors for TRALI in 89 cases compared with 164 matched transfused controls
[15]. The following pretransfusion TRALI risk factors were identified:
● Liver transplantation surgery ● Chronic alcohol abuse ● Shock ● Higher peak airway pressure
while being mechanically ventilated ● Current smoking ● Higher interleukin (IL)8 levels ● Positive
fluid balance In a nested casecontrol study evaluating patients in an intensive care unit (ICU) for more
than 48 hours, risk factors for TRALI/possible TRALI included emergency cardiac surgery, hematologic
malignancy, massive transfusion, sepsis, mechanical ventilation, and a high Acute Physiology and
Chronic Health Evaluation II (APACHE II) score [12]. In another study evaluating critically ill patients in
a medical ICU, sepsis, liver disease, and a history of alcohol abuse were more common in transfusion
recipients who developed TRALI/possible TRALI than in transfused controls without respiratory
compromise [13]. A Medicare database review (over 11 million patients, 2556 with a TRALI diagnosis
code) identified modestly higher rates of TRALI in recipients of platelet or plasmacontaining products
rather than red blood cells; females versus males; whites versus nonwhites; and individuals with
postinflammatory pulmonary fibrosis, smoking, or other medical illnesses in the prior six months [28].
Blood component risk factors — Virtually all blood components have been associated with TRALI. This
includes transfused whole blood derived platelets, cryoprecipitate [4], and granulocytes [30], as well as
intravenous immunoglobulin preparations [3133], and allogeneic stem cells [2,16,23,34].
●
Donor gender and highplasmavolume blood components — Though TRALI has been associated with
virtually all blood products, highplasmavolume components such as plasma, apheresis platelet
concentrates, and whole blood have been consistently shown to carry the greatest risk per component or
per transfusion episode [8,11,18,35]. The volume of plasma passively infused that results in TRALI is
unknown, but may be as small as 10 to 20 mL [36]. Further studies have demonstrated a role for female
sex and increased parity of the donor in the risk for TRALI [15,3739]. The role of these factors was
illustrated in a multicenter prospective cohort investigation utilizing active TRALI surveillance strategies,
which identified the following donor/blood component risk factors for TRALI [15]:
• Plasma or whole blood from female donors •
Increased volume of highly reactive transfused antihuman leukocyte antigen (HLA) Class II antibody
with specificity for a cognate recipient HLA antigen (ie, antibodies for which the recipient had the
corresponding HLA antigen)
• Increased volume of transfused antihuman neutrophil antigen (HNA) antibody [15]

The presence of noncognate antiHLA Class II antibodies, weaker cognate antiHLA Class II antibodies, or
any antiHLA Class I antibody were not associated with TRALI in this study. However, other case reports
suggest that antiHLA Class I antibodies can cause TRALI [8,40].
●
Red blood cell storage duration — Although a longer duration of red blood cell storage has been
suggested to increase the risk of TRALI, two randomized clinical trials and two large observational
studies have not confirmed this association [15,4144]. In aggregate, the available evidence suggests that
the duration of red blood cell storage is not a major risk factor in the development and/or severity of
TRALI.
PATHOGENESIS — The generally accepted theory for TRALI pathogenesis is that it occurs via a twohit
mechanism [4,45,46].
●
Neutrophil sequestration and priming – The first hit involves neutrophil sequestration and priming in the
lung microvasculature, due to recipient factors such as endothelial injury. Priming refers to shifting of
neutrophils to a state where they will respond to an otherwise innocuous or weak signal [47]. Endothelial
cells are thought to be responsible for both the neutrophil sequestration (through adhesion molecules) and
priming (through cytokine release). Generally these events are coupled and exist prior to the transfusion,
although there may be circumstances in which they can occur as a result of the transfusion. (See
'Recipient risk factors' above.)
●
Neutrophil activation – The second hit is activation of recipient neutrophils by a factor in the blood
product. Activation is associated with the release from neutrophils of cytokines, reactive oxygen species,
oxidases, and proteases that damage the pulmonary capillary endothelium. This damage causes
inflammatory (nonhydrostatic) pulmonary edema. Transfused factors responsible for host neutrophil
activation can include antibodies in the blood component directed against recipient antigens, or soluble
factors such as bioactive lipids that can activate neutrophils. Donor antileukocyte antibodies can bind to
antigens on recipient neutrophils or possibly to other cells such as monocytes or pulmonary endothelial
cells; this is referred to by some authors as immune TRALI [4852]. Bioactive lipids and other soluble
factors in the transfused blood component can act as biological response modifiers (BRMs); TRALI
resulting from these nonantibody BRMs is sometimes referred to as nonimmune TRALI [46]. (See 'Blood
component risk factors' above.)
Clinical observations supporting the twohit theory come from retrospective studies demonstrating that
most transfused blood products containing HLA antibody do not cause TRALI, even if a cognate recipient
antigen is present [53]. In retrospective studies, TRALI was detected in only 2.9 percent of individuals
who received blood products from donors previously implicated in causing TRALI [40,5356].
In one case of fatal TRALI, the implicated donor was a multiparous female who had made 290 previous
plasma apheresis donations [9]. Of 36 patients who had received her plasma in the prior two years, 15
experienced transfusion reactions with pulmonary symptoms, and 21 (58 percent) did not, again
highlighting that factors from the transfusion alone are insufficient to cause TRALI. In this case, the
donor had antibodies against a leukocyte antigen (HNA3a) present in more than 95 percent of the general
population that has been associated with severe often fatal TRALI cases [57]. In another case, TRALI
occurred in a recipient of a single lung transplant only in the transplanted lung, and one of the blood
products the donor received contained antiHLA Class I antibodies that matched an HLA antigen present
only in the transplanted lung [58].
The proportion of TRALI caused by antibodies versus BRMs remains undetermined and is likely to vary
by the type of component transfused, with antibodymediated mechanisms explaining the majority of the
cases due to plasma, and nonimmune BRMs responsible for most cases from red blood cell transfusion
[18,59,60]. The widely stated statistic that 80 to 85 percent of TRALI cases are due to the
antibodymediated mechanism is likely influenced by publication bias [61]. Of note, a case series
comparing BRMmediated TRALI with antibodymediated TRALI suggests that BRMmediated TRALI is
a less severe condition [46].
A second model related to the twohit theory is the threshold model. This model agrees that two hits are
usually necessary for TRALI, but allows for the possibility that in some cases the second hit is so strong
that

an initial priming event is not required [46,62,63]. This theory explains TRALI cases that have occurred
in otherwise healthy individuals who have received fresh frozen plasma (FFP) as a treatment for reversing
warfarin anticoagulation.
Several observations support the role of neutrophils as the major effector cells in TRALI. Neutrophil
activation occurs in animal models of TRALI [6469]. Transient neutropenia indicative of pulmonary
sequestration has been seen in patients in the early phase of TRALI, whereas TRALI is rarely seen in
neutropenic patients [40,7074]. In an autopsy case, postmortem examination within two hours of TRALI
onset revealed aggregates of neutrophils within the pulmonary capillaries associated with inflammatory
edema and endothelial injury [75].
Multiple mechanisms of neutrophil activation in TRALI have been proposed. As an example, antibodies
to human leukocyte antigen (HLA) Class I and human neutrophil antigens (HNA) may bind to recipient
neutrophils and trigger their activation [62,63,76,77]. It has been known for years that female donors, due
to exposure to fetal alloantigens during pregnancy, have a much higher prevalence of antiHLA antibodies
than do male donors [78,79]. While antiHNA antibodies account for only a small percentage of TRALI
cases from most countries (<5 percent), in Germany these constitute a higher percentage (28 percent in
one series) [19]. Antibodies directed against the HNA 3a antigen have been associated with a substantial
number of severe or fatal TRALI cases [80,81].
TRALI can also be associated with donor antibodies directed against HLA Class II, which is primarily
expressed on antigenpresenting cells [47,63]. These antibodies may bind to HLA Class II antigens on
monocytes, causing release of cytokines that in turn activate primed neutrophils [77,8284].
When the second hit for neutrophil activation is a biological response modifier (BRM) rather than an
antibody, the BRM is believed to activate neutrophils directly. Most of the work implicating these
substances has come from in vitro and animal studies, and has implicated lysophosphatidylcholines (from
white blood cells and platelets), neutral lipids (from the breakdown of red cell membranes), and soluble
CD40 ligand (which accumulates in stored platelet concentrates) in neutrophil activation
[4,24,45,67,68,8587].
CLINICAL PRESENTATION — The characteristic clinical presentation of TRALI is the sudden onset of
hypoxemic respiratory insufficiency during or shortly after the transfusion of a blood product (table 1)
[1,2]. Symptoms may be delayed as long as six hours, but usually begin within one to two hours of
initiating the blood component infusion [1,23]. Indeed, the majority of cases occur within minutes of
initiating a transfusion [4]. A number of additional signs and symptoms associated with noncardiogenic
pulmonary edema and inflammation have been reported [1,18,23,73,74,88,89]. As an example, in a
retrospective study of 49 TRALI cases, the most common signs and symptoms and their approximate
frequencies were as follows [18]:
●
Hypoxemia: in an intubated patient this could manifest as a change in oxygenation or increased oxygen
requirements (100 percent, by definition)
●
Pulmonary infiltrates on chest radiography (100 percent, by definition; the cardiac silhouette is classically
normal)
● If previously intubated, pink frothy airway secretions from the endotracheal tube (56 percent) ● Fever
(33 percent) ● Hypotension (32 percent) ● Cyanosis (25 percent) Other reports have also noted
tachypnea, tachycardia, and elevated peak and plateau airway pressures in intubated patients. An acute,
transient drop in the peripheral neutrophil count (consistent with sequestration of large numbers of
neutrophils in the lungs) has also been reported.
DIAGNOSIS — TRALI should be considered whenever a patient develops hypoxemic respiratory
insufficiency during or shortly after transfusion of any blood product [1]. TRALI is a clinical diagnosis
made using the criteria outlined by the NHLBI’s working group on TRALI as well as the Canadian
Consensus Conference on TRALI (table 1) [1,2]. These criteria require the presence of new ALI/ARDS
occurring during or within six hours after blood product administration, documented by hypoxemia and
an abnormal chest radiograph. Hypoxemia is documented when oxygen saturation is ≤90 percent on room
air or the PaO2/FIO2

ratio is <300 mmHg, although other signs of hypoxia can also satisfy this criterion. Frontal chest
radiograph must demonstrate bilateral pulmonary infiltrates. (See "Noncardiogenic pulmonary edema",
section on 'Definition of noncardiogenic pulmonary edema' and "Acute respiratory distress syndrome:
Clinical features and diagnosis in adults".)
When a clear temporal relationship to an alternative risk factor for ALI/ARDS coexists, a formal
diagnosis of TRALI cannot be made. In these circumstances, "possible TRALI" is the more appropriate
diagnosis. Use of these separate diagnostic categories (ie, TRALI and possible TRALI) allows for their
separate reporting in surveillance systems, which may facilitate differential approaches to donor
investigation and management, as well as targeting research programs to either (or both) groups of
patients. (See 'Differential diagnosis' below.)
When TRALI is suspected, the treating physician should evaluate the recipient’s vital signs, assess the
extent of hypoxemia, and obtain a chest radiograph. Pulse oximetry is often sufficient, but arterial blood
gas analysis may be warranted in more severe cases. Consideration of the likelihood of other potential
causes for the respiratory distress (eg, cardiovascular compromise, anaphylaxis, sepsis, exacerbation of
underlying lung disease or atelectasis) should guide appropriate clinicianinitiated laboratory testing. (See
'Differential diagnosis' below.)
When a transfusion reaction such as TRALI is suspected, the transfusion should be stopped immediately
and the case should be promptly reported to the hospital transfusion medicine service/blood bank. Based
on the details of the case, the blood bank will initiate a transfusion reaction workup, which will usually
include drawing a sample from the patient for appropriate laboratory tests. These may include complete
blood count, bilirubin, haptoglobin, direct antiglobulin (Coombs) test, brain natriuretic peptide (BNP) or
Nterminal (NT) ProBNP, and HLA antigen typing. (See "Natriuretic peptide measurement in heart
failure".)
If TRALI is suspected, the blood bank will compile a list of blood products transfused within the previous
six hours and forward this list to the blood supplier. The blood supplier will then follow its procedures to
recall these donors and initiate testing for HLA and possibly HNA antibodies. However, these results will
not be available for several weeks. Identifying the implicated donor(s) and deferring that individual from
future high plasma volume donation requires cooperation between the clinician (to provide accurate
clinical information), the hospital transfusion medicine service, and the blood supplier. (See 'Prevention'
below.)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of TRALI includes other conditions that can
manifest with respiratory distress following transfusion. This includes other causes of ALI/ARDS as well
as other transfusion reactions. These conditions are described in more detail in the following sections.
Possible TRALI — A formal diagnosis of TRALI requires the absence of temporal relationships with
additional risk factors for ALI/ARDS, such as aspiration, pneumonia, toxic inhalation, lung contusion,
trauma, burn injury, and pancreatitis. When other criteria for TRALI are met but additional risk factors for
ALI/ARDS are also present (table 1), a diagnosis of TRALI cannot be made and the term "possible
TRALI" is preferred. This can also be designated as TRALI with ALI risk factors. Although massive
transfusion has historically been recognized as a risk factor for ALI/ARDS, a diagnosis of TRALI should
be made in this circumstance provided that no other ALI/ARDS risk factors were present.
TACO — Transfusionassociated circulatory overload (TACO) is another cause of transfusionrelated
respiratory insufficiency. Though it is most commonly reported in elderly patients and small children,
TACO can occur in all age ranges. Additional risk factors for TACO include compromised cardiac
function, positive fluid balance, and rapid blood product administration. TACO appears to occur more
frequently in surgical or intensive care settings, where large fluid volumes and blood are administered.
Characteristic features and differentiating factors for TRALI versus TACO are shown in the table (table
2) [90]. (See "Transfusion reactions caused by chemical and physical agents", section on 'Transfusional
volume overload (TACO)'.)
As a general rule, TRALI is more likely to be associated with fever, hypotension, and exudative
pulmonary infiltrates, and less likely to respond to diuresis. In contrast, TACO is more likely to be
associated with findings suggesting volume overload (eg, positive fluid balance, elevated jugular venous
pressure, elevated pulmonary artery occlusion pressure) or poor cardiac function (eg, history of
congestive heart failure, reduced left ventricular ejection fraction, or diastolic dysfunction). Similarly,
elevated systolic blood pressures

near the time of dyspnea onset, a widened pulmonary vascular pedicle width or increased cardiothoracic
ratio on chest radiography, and/or increased circulating levels of brain natriuretic peptide (BNP) or N
terminal (NT)ProBNP suggest a diagnosis of TACO rather than TRALI [9196]. (See "Natriuretic peptide
measurement in heart failure".)
Differentiating TRALI from TACO can be a significant challenge, particularly as both may coexist
[91,97,98]. In such cases, pulmonary findings may be due to a combination of hydrostatic (eg, TACO)
and non hydrostatic (eg, TRALI) lung edema. Indeed, studies show that approximately 30 percent of
ALI/ARDS patients have at least mild evidence of left atrial hypertension [99]. In these circumstances,
ALI/ARDS is diagnosed in the presence of fluid overload based on clinical judgment that the degree of
fluid overload is not sufficient to explain the extent of hypoxemia and pulmonary infiltrates. This type of
mixed picture may be more likely to occur in intensive care unit (ICU) patients.
Other causes of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) — ALI/ARDS may
be present prior to the initiation of transfusion therapies or may arise more than six hours after a
transfusion episode. In these cases, ARDS is the more appropriate diagnosis. Of note, a consensus
conference has recommended eliminating the term ALI, which has historically described lung injury with
less severe hypoxemia (ie, PaO 2 /FiO 2
<300 but >200). Rather, it is now recommended that such cases be classified
as "mild ARDS" [100]. In such cases, it is recognized that the administration of blood products may in
fact contribute to ALI/ARDS development even though a formal diagnosis of TRALI cannot be made.
(See "Acute respiratory distress syndrome: Clinical features and diagnosis in adults".)
Other transfusion reactions
●
Hemolytic transfusion reactions – Hemolytic transfusion reactions can cause respiratory distress, but fever
and chills tend to predominate in hemolytic transfusion reactions more than in TRALI. Hemolytic
reactions are typically due to ABO incompatibility, and pink serum or hemoglobinuria may be seen due to
intravascular hemolysis. The direct antiglobulin (Coombs) test will be positive in hemolytic reactions, but
not in TRALI. (See "Transfusionassociated immune and non immunemediated hemolysis" and
"Immunologic blood transfusion reactions", section on 'Acute hemolytic reactions'.)
●
Anaphylaxis – Anaphylaxis can cause respiratory distress similar to TRALI, but anaphylaxis is more
often associated with airway signs and symptoms such as stridor, cough, wheezing, nasal congestion, and
bronchospasm. Anaphylaxis is also more often associated with a new rash, gastrointestinal symptoms
such as nausea and/or vomiting, and shock. Notably, however, the latter may be seen in TRALI as well.
The cause of most transfusionassociated anaphylactic reactions is unknown, but one recognized etiology
is transfusion of IgAcontaining products to an IgA deficient recipient who has antibodies to IgA. (See
"Immunologic blood transfusion reactions", section on 'Anaphylactic reactions' and "Anaphylaxis: Rapid
recognition and treatment".)
●
Sepsis – Severe sepsis and septic shock are often associated with respiratory distress, fever, and
hypotension. Evidence for an active infectious process (leukocytosis, fever, positive microbiology)
suggests the diagnosis of severe sepsis or septic shock rather than TRALI. Transfusionassociated sepsis is
generally associated with the administration of bacterially contaminated platelets. In this case, evaluation
of the transfusion by the blood bank will typically identify a contaminating microorganism. (See "Clinical
and laboratory aspects of platelet transfusion therapy", section on 'Complications of platelet transfusion'.)
TREATMENT
Overview — If TRALI/possible TRALI is suspected, the transfusion should be discontinued immediately.
Physicians should alert the blood bank and initiate an evaluation for a transfusion reaction. This is
important for the protection of future recipients as well as for TRALI laboratory testing and workup. This
initial evaluation is described in more detail above. (See 'Diagnosis' above.)
Management of the patient with TRALI/possible TRALI is supportive, with oxygen supplementation for
the correction of hypoxemia being the cornerstone of treatment. Noninvasive respiratory support with
continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) may be
sufficient in

less severe cases, but endotracheal intubation with invasive mechanical ventilation is often required [13].
The available evidence suggests that most patients who develop either TRALI or possible TRALI will
require ventilatory support (approximately 70 to 80 percent) [5,12,13,101].
Ventilation — There have been no prospective clinical investigations on strategies for managing
mechanical ventilation in patients with TRALI, and it is generally believed that ventilator management
should be guided by the same principles used in patients with other forms of ALI/ARDS [102]. The
successful application of more extreme life support interventions, such as extracorporeal membrane
oxygenation, has also been described in TRALI [103]. (See "Acute respiratory distress syndrome:
Supportive care and oxygenation in adults" and "Mechanical ventilation of adults in acute respiratory
distress syndrome" and "Extracorporeal membrane oxygenation (ECMO) in adults".)
Hemodynamic support — Patients with TRALI often present with hypovolemia and associated
hypotension [104]. The initial goal of hemodynamic management is to ensure adequate endorgan
perfusion. This may be achieved with fluid resuscitation and/or vasoactive support. Caution should be
taken with early empiric administration of diuretic therapy, as it may result in hypotension in those who
were initially hemodynamically stable [16,105]. However, for patients with sustained hypoxemia and
demonstrated hemodynamic stability, administration of diuretic therapy may be a reasonable intervention.
(See "Treatment of severe hypovolemia or hypovolemic shock in adults" and "Evaluation and
management of severe sepsis and septic shock in adults", section on 'Interventions to restore perfusion'.)
Steroids — Intravenous corticosteroids have been extensively studied in the setting of ALI/ARDS with
mixed results [16,106,107]. In regards to TRALI, there are isolated case reports supporting highdose
corticosteroids in the treatment of this syndrome [16,108]. However, the efficacy of corticosteroids has
not been tested in prospective clinical studies, and the limited anecdotal evidence is unconvincing. Thus,
we do not recommend the routine use of corticosteroids when TRALI is suspected. Moreover, due to
evidence suggesting harm when initiating corticosteroids late in the course of ALI/ARDS (>14 days after
syndrome onset) [16,105,109], we advise against the use of corticosteroid therapy when the lung injury is
fully established and has been present for more than two weeks. (See "Acute respiratory distress
syndrome: Novel therapies in adults", section on 'Glucocorticoids'.)
Investigational strategies — In addition to the therapies described above, a number of additional
ALI/ARDS and, by association, TRALI treatment and prevention strategies have been proposed and are
under various stages of investigation. Examples include HMGCoA reductase inhibitors (statins) [110],
aspirin [110,111], and alternatives to allogeneic blood products (eg, RBC substitutes, prothrombin
complex concentrates, fibrinogen concentrates, and activated factor VII). However, at present, none of
these therapies has sufficient evidence to justify its use as a routine TRALI prevention or treatment
measure.
Additional transfusions — Patients who recover from TRALI do not appear to be at increased risk for
recurrent episodes following transfusions from other donors; however, published experience is limited.
Survivors of TRALI can receive additional blood products in the future, and transfusion of needed blood
products should not be withheld [16,23]. Importantly, however, individuals should not receive plasma
containing blood products from the implicated donor [112115].
PROGNOSIS — Initial descriptions detailing the clinical course for TRALI suggested quick resolution of
hypoxemia, generally within 24 to 48 hours of symptom onset [5]. However, the majority of patients who
develop TRALI will require ICU admission and ventilator support [12,13]. For those requiring
mechanical ventilation, these early reports described a mean duration of ventilatory support lasting
approximately 40 hours [5]. In contrast, subsequent evidence suggests that most cases will require
respiratory support for a longer period (eg, approximately 3 to 10 days) [12,13]. These more
contemporary data frequently report composite outcomes from cases of TRALI and possible TRALI and
limit the study population to the critically ill. Such cases are likely to represent the more severe end of the
clinical spectrum. In contrast, milder cases of TRALI and/or possible TRALI may go undiagnosed or
unreported. As such, the clinical presentation, need for lifesupport interventions, and outcomes for
patients with TRALI and/or possible TRALI remain incompletely defined.
Mortality rates associated with TRALI/possible TRALI have been reported to be as high as 41 to 67
percent

[7,12,13,101]. Again, however, these more extreme reports generally originate from critically ill study
populations with TRALI and possible TRALI combined into a single composite outcome. In contrast,
lower mortality rates (5 to 10 percent) are typically described for TRALI itself [21,116]. Although limited
information is available, it appears that most survivors will recover to their baseline pulmonary function,
and they can safely receive additional blood products in the future [1,16,23]. (See "Acute respiratory
distress syndrome: Supportive care and oxygenation in adults".)
PREVENTION — Following all cases of TRALI and some cases of possible TRALI, the blood bank and
the blood collection facility should investigate all of the associated donors for the presence of antihuman
leukocyte antigen (HLA) and possibly antihuman neutrophil antigen (HNA) antibodies [117], with the
goal of identifying donors who should be deferred from future donations. In reality, the number of donors
investigated may be more limited and the laboratory workup performed by transfusion services may vary
depending upon the number of donors in a case; the availability of donor samples; the availability of
neutrophil antibody testing, which is restricted to a few specialty laboratories in the US; and the
availability of a recipient sample for HLA antigen typing [1,118,119]. Some laboratories in Europe also
perform leukocyte crossmatching as part of the evaluation [117].
A donor who is shown to have leukocyte antibodies that match or are likely to match a recipient’s
leukocyte antigens is classified as an implicated donor and is, at minimum, deferred from future plasma
apheresis or platelet apheresis. Furthermore, most blood banks will defer an implicated donor from any
type of blood donation; this is particularly true if the donor has antiHNA 3a [1].
In addition, several general blood donor management strategies are in use to reduce the incidence of
TRALI [1,8,35,118,120132]:
●
Adherence to current guidelines of blood component utilization, especially for plasma, to decrease
recipient exposure to transfused units.
● Deferral of donors implicated in a TRALI reaction. ●
For high plasma volume components (eg, FFP, plasma frozen within 24 hours of phlebotomy [FP24],
plasma, cryoreduced [cryopoor] plasma, apheresis platelets, buffy coat derived platelet pools resuspended
in plasma from a single donor, and whole blood), selection of donors who are less likely to be
alloimmunized to leukocytes.
● Use of pooled solvent detergent plasma as an alternative to FFP. ● Testing of parous apheresis donors
of platelets or plasma for antiHLA antibodies. Deferral of multiparous female donors — It has been well
established that donors implicated in TRALI cases are more likely to be female and more likely to be
multiparous [15,38,39]. These factors resulted in the implementation of a new TRALI risk mitigation
policies during the mid to late 2000s throughout most of Europe and the United States, in which
transfusable plasma units were predominantly obtained from male donors, thereby avoiding the
transfusion of plasma units from female donors [8,11,123125,133]. This policy is feasible for plasma
transfusion because the number of plasma units derived from whole blood or apheresis collections is in
excess of demand. In contrast, this policy is not feasible for apheresis platelet transfusion where
restriction of units to male donors would seriously jeopardize the platelet supply.
The importance of these policies is illustrated by a large multicenter study conducted under the auspices
of the National Heart, Lung, and Blood Institute (NHLBI) Retrovirology and Donor Epidemiology
Program II (REDSII) [131]. This study, known as the Leukocyte Antibody Prevalence Study (LAPS),
used modern flow cytometry techniques to assess the prevalence of HLA antibodies in almost 8000
volunteer blood donors. There was a doseresponse increase in the frequency of antiHLA antibodies
according to parity, from 1.7 percent for never pregnant females to 32.2 percent for four or more
pregnancies. Donors who themselves had received a blood transfusion, males, and never pregnant female
donors all showed very low frequency of antiHLA antibodies (in the range of 1 to 2 percent) [131,134].
These data suggest that TRALI risk mitigation programs do not need to exclude plasma from never
pregnant females or from donors with a previous transfusion history [125]. Nevertheless, some European
countries do not transfuse plasma obtained from donors who have themselves received a transfusion
[123]. These data also have helped to guide policies for HLA antibody testing of selected subpopulations
of female plasma and platelet apheresis

donors.
The following observations support the effectiveness of sexbased risk reduction policies for reducing
TRALI incidence from plasma transfusion:
●
The UK National Blood Service, starting in late 2003, provided 80 to 90 percent of FFP from male
donors. This was associated with a significant decrease in the risk of highly likely/probable TRALI due to
FFP (from 15.5 per million units issued from 1999 to 2004 to 3.2 per million from 2005 to 2006) [8].
There were 23 highly likely/probable TRALI cases from all components in 2003, compared with three in
2010 [124].
●
In a fouryear nested casecontrol study conducted from 2006 to 2009 at the University of California San
Francisco and Mayo Clinic, TRALI incidence in 2006 (prior to implementation of risk reduction
methods) was 0.0257 percent (1 in 3891); in 2009, after implementation of risk reduction policies for
plasma products, TRALI incidence decreased to 0.0081 percent (1 in 12,345) [15].
●
In the US, annual TRALI fatalities attributed to plasma transfusion and reported to the FDA declined
from a peak of 23 cases in 2006 to three cases in 2011 [3]. In the three years prior to introduction of the
sexbased TRALI risk reduction policies, plasma accounted for 48 percent of the fatal cases reported to
Food and Drug Administration (FDA), compared with 27 percent in the four years following their
implementation (2008 to 2011). Similarly, cases of suspected TRALI from plasma reported to the
American Red Cross National Hemovigilance Program decreased from a rate of approximately 20
probable TRALI cases per million plasma components in 2006 to approximately four per million plasma
components in 2008. Moreover, in contrast to six TRALI fatalities related to plasma transfusion in 2006,
there were none in 2008 [11].
●
In Germany, antibodymediated TRALI from FFP transfusion decreased following the implementation of
TRALI risk reduction policies. The rate fell from 12.71 per million units in 2006 to 2007 (pre
implementation of risk reduction policies) to 6.81 per million units in 2008 to 2009, during which there
was partial implementation of risk reduction policies. With full implementation in 2010, no cases were
reported [135].
Use of solvent detergent treated plasma — Another strategy for TRALI risk reduction is to transfuse a
pooled solvent detergent plasma product (S/D plasma) in place of FFP. An S/D plasma product was
approved by the United States Food and Drug Administration in 2013, and S/D plasma has been widely
used in many European countries for many years. Notably, observational data from over 10 million S/D
plasma unit transfusions support the conclusion that this product does not cause TRALI [127]. A more
controlled data set was provided by hemovigilance data collected in France in 2007 and 2008 [35]. After
transfusion of 212,000 S/D plasma units, there were no TRALI cases associated solely with S/D plasma.
In contrast, the TRALI incidence rate from FFP transfusion was 1 in 31,000 units. The absence of TRALI
following transfusion of S/D plasma has been attributed to the pooling of plasma from many different
donors, resulting either in dilution of antiHLA antibodies or in binding of such antibodies by soluble HLA
antigens [126,128]. Notably, studies on 32 batches of SD plasma were unable to detect the presence of
HLA antibodies in this product [126]. See Solvent/detergenttreated fresh frozen plasma drug information.
(See "Pathogen inactivation of blood products", section on 'Solventdetergent method'.)
Mitigating TRALI risk from platelets — Some blood centers have implemented a policy of testing
selected populations of platelet apheresis donors (eg, previously pregnant females, depending on the
number of pregnancies) for antiHLA antibodies and then redirecting antiHLA antibody positive donors
away from all highplasmavolume donations, including platelet apheresis [125]. However, this strategy has
not been universally adopted, and thus far there are no adequate data to evaluate its effect on TRALI
incidence [123]. Another strategy considered for apheresis platelets is to resuspend the platelets in platelet
additive solution (PAS) [123]. This reduces the plasma volume of the product by twothirds. However, it is
not currently known whether TRALI risk from the reduced plasma volume (still approximately 100 mL of
plasma) will be decreased.
Mitigating TRALI risk from RBC — Due to the success of TRALI risk reduction measures for plasma,
the relative percentage of TRALI cases from red blood cells (RBC) has increased, such that the majority
of

current TRALI cases are associated with RBC transfusion [126]. TRALI risk reduction measures appear
to have had no effect on the frequency of TRALI cases associated with RBC transfusion [3,126,136].
Data suggest that a nonantibody mediated mechanism, presumably a soluble biologic response modifier,
may account for the majority of TRALI cases caused by RBC transfusion [18,59,60]. In one case series,
donor antibodies directed against cognate recipient antigens were identified less frequently in TRALI
cases involving only RBC transfusions (18 percent) than in cases involving FFP (82 percent) [18]. Two
subsequent analyses found that TRALI cases associated with RBC transfusion were not correlated with
female or other alloimmunized donors. In contrast, these studies did associate highplasma volume blood
components from female and alloimmunized plasma donors with risk for TRALI [18,59].
Although RBC mediated TRALI continues to occur, no effective and practical risk reduction measures are
available, with the exception of conservative RBC transfusion practices.
One retrospective report suggested that leukocyte reduction may have decreased TRALI incidence at a
single institution; however, a randomized clinical trial comparing prestorage leukocyte reduced RBC
transfusion with standard allogeneic RBC transfusion found no evidence for differing rates of either early
or late ALI/ARDS in transfused trauma patients [137,138]. Furthermore, TRALI has been reported in
many countries that practice universal leukoreduction [123].
Based on the mechanism for red blood cellinduced TRALI, it has been suggested that the use of younger
red blood cells or washed red blood cells would prevent some TRALI cases [123,139]. However, the data
on red blood cell age and TRALI are contradictory and unconvincing. Moreover, the only data concerning
prevention of TRALI by RBC washing are retrospective and observational. [4244,68,123]. Furthermore,
washing large number of red cell units is not logistically feasible for most institutions.
A novel approach to TRALI mitigation utilizing a prototype prestorage leukoreduction filter has also been
described [52]. This filter removes platelets and plasma proteins such as IgG from the filtered units in
addition to leukocytes. An initial evaluation in an animal model system suggested that TRALI incidence
from transfused RBC units was reduced with this filter. However, much more work is needed before this
approach is ready for clinical testing.
SUMMARY AND RECOMMENDATIONS
●
Transfusionrelated acute lung injury (TRALI) is a serious respiratory complication of transfusion. It is the
leading cause of transfusionrelated mortality in the United States. (See 'Prognosis' above.)
●
TRALI can be seen following transfusion of any type of blood component in any patient. Historically, the
blood components most likely to cause TRALI were those with a high concentration of donor plasma (due
to antibodies to human leukocyte and human neutrophil antigens). Risk mitigation strategies have
dramatically reduced the risk of plasmaassociated TRALI, and currently the majority of TRALI cases are
associated with transfusion of red blood cells (RBC). (See 'Epidemiology' above and 'Prevention' above.)
●
A "twohit" hypothesis for the pathogenesis of TRALI holds that recipient neutrophils are primed for
activation by virtue of the patient's underlying clinical condition. The second hit involves activation of
these neutrophils by preformed antileukocyte antibodies or biological response modifiers contained in the
transfused product. In rare cases, the transfused product may provide both hits. (See 'Pathogenesis'
above.)
●
The characteristic clinical presentation of TRALI is the sudden onset of hypoxemic respiratory
insufficiency during or shortly after the transfusion of a blood product. Patients with TRALI often have
frothy airway secretions (if intubated), fever, cyanosis, and hypotension. When TRALI is suspected, the
treating physician should evaluate the recipient’s vital signs, assess the extent of hypoxemia, and obtain a
chest radiograph. Pulse oximetry is often sufficient, but arterial blood gas analysis may be warranted in
more severe cases. (See 'Clinical presentation' above.)
●
TRALI is a clinical diagnosis. It should be considered whenever a patient develops hypoxemic respiratory
distress during or within six hours after transfusion of any blood product. The criteria set
psedTimeMs=0&source=sea... 10/20

forth by the United States National Heart, Lung, and Blood Institute and the Canadian Consensus
Conference panels should be considered sufficient to establish the diagnosis of TRALI (table 1). These
criteria require the presence of new acute lung injury (ALI)/acute respiratory distress syndrome (ARDS)
occurring during or within six hours after blood product administration. (See 'Diagnosis' above.)
●
The differential diagnosis of TRALI includes other conditions that can manifest with respiratory distress
following transfusion. This includes other causes of ALI/ARDS as well as other transfusion reactions.
The distinction between TRALI and TACO is important for proper management (table 2). Since a
confirmed diagnosis of TRALI has implications for blood suppliers, the term "possible TRALI" is
preferred for patients who meet criteria for TRALI, but have additional risk factors for ALI/ARDS. (See
'Differential diagnosis' above.)
●
Management of the patient with TRALI includes immediate discontinuation of the transfusion and
reporting to the blood bank that TRALI is suspected. Therapy is supportive with supplemental oxygen
and ventilatory support with lung protective strategies when clinically indicated. Clinical improvement
should be expected to occur spontaneously as the lung injury resolves, and patients who survive TRALI
are expected to recover completely. (See 'Treatment' above and 'Prognosis' above.)
●
Prevention of TRALI involves deferring donors implicated in a case of TRALI from future platelet
apheresis, plasma apheresis, and possibly also whole blood donation. Donations from multiparous women
are most likely to contain antileukocyte antibodies. Most developed countries have adopted a policy of
supplying transfusable plasma products (plasma, platelets, and whole blood) exclusively or predominantly
from male donors, female donors with no prior pregnancy, or from donors who test negative for
HLAantibodies. (See 'Prevention' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusionrelated acute lung
injury: statement of a consensus panel. Transfusion 2004; 44:1774. 2. Toy P, Popovsky MA, Abraham
E, et al. Transfusionrelated acute lung injury: definition and review.
Crit Care Med 2005; 33:721. 3. Fatalities Reported to FDA Following Blood Collection and
Transfusion: Annual Summary for Fiscal
Year 2011. Available at:
http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFat
alities/ucm302847.htm (Accessed on December 28, 2012). 4. Silliman CC, Boshkov LK,
Mehdizadehkashi Z, et al. Transfusionrelated acute lung injury:
epidemiology and a prospective analysis of etiologic factors. Blood 2003; 101:454. 5. Popovsky MA,
Moore SB. Diagnostic and pathogenetic considerations in transfusionrelated acute
lung injury. Transfusion 1985; 25:573. 6. Wallis JP. Transfusionrelated acute lung injury
(TRALI)underdiagnosed and underreported. Br J
Anaesth 2003; 90:573. 7. Rana R, FernándezPérez ER, Khan SA, et al. Transfusionrelated acute lung
injury and pulmonary
edema in critically ill patients: a retrospective study. Transfusion 2006; 46:1478. 8. Chapman CE,
Stainsby D, Jones H, et al. Ten years of hemovigilance reports of transfusionrelated acute lung injury in
the United Kingdom and the impact of preferential use of male donor plasma. Transfusion 2009; 49:440.
9. Kopko PM, Marshall CS, MacKenzie MR, et al. Transfusionrelated acute lung injury: report of a
clinical lookback investigation. JAMA 2002; 287:1968. 10. Vlaar AP, Wortel K, Binnekade JM, et
al. The practice of reporting transfusionrelated acute lung injury:
a national survey among clinical and preclinical disciplines. Transfusion 2010; 50:443. 11. Eder AF,
Herron RM Jr, Strupp A, et al. Effective reduction of transfusionrelated acute lung injury risk
with malepredominant plasma strategy in the American Red Cross (20062008). Transfusion 2010;
50:1732. 12. Vlaar AP, Binnekade JM, Prins D, et al. Risk factors and outcome of transfusionrelated
acute lung

injury in the critically ill: a nested casecontrol study. Crit Care Med 2010; 38:771. 13. Gajic O, Rana
R, Winters JL, et al. Transfusionrelated acute lung injury in the critically ill: prospective
nested casecontrol study. Am J Respir Crit Care Med 2007; 176:886. 14. Finlay HE, Cassorla L,
Feiner J, Toy P. Designing and testing a computerbased screening system for
transfusionrelated acute lung injury. Am J Clin Pathol 2005; 124:601. 15. Toy P, Gajic O, Bacchetti
P, et al. Transfusionrelated acute lung injury: incidence and risk factors.
Blood 2012; 119:1757. 16. Looney MR, Gropper MA, Matthay MA. Transfusionrelated acute lung
injury: a review. Chest 2004;
126:249. 17. Vlaar AP, Hofstra JJ, Determann RM, et al. The incidence, risk factors, and outcome of
transfusion
related acute lung injury in a cohort of cardiac surgery patients: a prospective nested casecontrol study.
Blood 2011; 117:4218. 18. van Stein D, Beckers EA, Sintnicolaas K, et al. Transfusionrelated acute lung
injury reports in the
Netherlands: an observational study. Transfusion 2010; 50:213. 19. KellerStanislawski B, Reil A,
Günay S, Funk MB. Frequency and severity of transfusionrelated acute
lung injuryGerman haemovigilance data (20062007). Vox Sang 2010; 98:70. 20. Holness L, Knippen
MA, Simmons L, Lachenbruch PA. Fatalities caused by TRALI. Transfus Med Rev
2004; 18:184. 21. Popovsky MA, Chaplin HC Jr, Moore SB. Transfusionrelated acute lung injury: a
neglected, serious
complication of hemotherapy. Transfusion 1992; 32:589. 22. Lieberman L, Petraszko T, Yi QL, et al.
Transfusionrelated lung injury in children: a case series and
review of the literature. Transfusion 2014; 54:57. 23. Silliman CC, Ambruso DR, Boshkov LK.
Transfusionrelated acute lung injury. Blood 2005; 105:2266. 24. Silliman CC, Paterson AJ, Dickey WO,
et al. The association of biologically active lipids with the
development of transfusionrelated acute lung injury: a retrospective study. Transfusion 1997; 37:719.
25. Gajic O, Rana R, Mendez JL, et al. Acute lung injury after blood transfusion in mechanically
ventilated
patients. Transfusion 2004; 44:1468. 26. Toy P, Gajic O. Transfusionrelated acute lung injury.
Anesth Analg 2004; 99:1623. 27. Watkins TR, Cooke CR, Hudson LD, et al. Transfusion and lung injury:
The role of red blood cell
storage time. Crit Care Med 2007; 35:A159. 28. Menis M, Anderson SA, Forshee RA, et al.
Transfusionrelated acute lung injury and potential risk
factors among the inpatient US elderly as recorded in Medicare claims data, during 2007 through 2011.
Transfusion 2014; 54:2182. 29. Benson AB, Austin GL, Berg M, et al. Transfusionrelated acute lung
injury in ICU patients admitted
with gastrointestinal bleeding. Intensive Care Med 2010; 36:1710. 30. Sachs UJ, Bux J. TRALI after
the transfusion of crossmatchpositive granulocytes. Transfusion 2003;
43:1683. 31. Suassuna JH, da Costa MA, Faria RA, Melichar AC. Noncardiogenic pulmonary edema
triggered by
intravenous immunoglobulin in cancerassociated thrombotic thrombocytopenic purpurahemolytic uremic
syndrome. Nephron 1997; 77:368. 32. Rizk A, Gorson KC, Kenney L, Weinstein R. Transfusionrelated
acute lung injury after the infusion of
IVIG. Transfusion 2001; 41:264. 33. Quest GR, Gaal H, Clarke G, Nahirniak S. Transfusionrelated
acute lung injury after transfusion of
pooled immune globulin: a case report. Transfusion 2014; 54:3088. 34. Boshkov LK.
Transfusionrelated acute lung injury and the ICU. Crit Care Clin 2005; 21:479. 35. Ozier Y, Muller JY,
Mertes PM, et al. Transfusionrelated acute lung injury: reports to the French
Hemovigilance Network 2007 through 2008. Transfusion 2011; 51:2102. 36. Win N, Chapman CE,
Bowles KM, et al. How much residual plasma may cause TRALI? Transfus Med
2008; 18:276. 37. Palfi M, Berg S, Ernerudh J, Berlin G. A randomized controlled trial
oftransfusionrelated acute lung
injury: is plasma from multiparous blood donors dangerous? Transfusion 2001; 41:317. 38. Wright
SE, Snowden CP, Athey SC, et al. Acute lung injury after ruptured abdominal aortic aneurysm repair: the
effect of excluding donations from females from the production of fresh frozen plasma. Crit Care Med
2008; 36:1796.

39. Gajic O, Yilmaz M, Iscimen R, et al. Transfusion from maleonly versus female donors in critically ill
recipients of high plasma volume components. Crit Care Med 2007; 35:1645. 40. Toy P, HollisPerry
KM, Jun J, Nakagawa M. Recipients of blood from a donor with multiple HLA antibodies: a lookback
study of transfusionrelated acute lung injury. Transfusion 2004; 44:1683. 41. Koch CG, Li L, Sessler DI,
et al. Duration of redcell storage and complications after cardiac surgery. N
Engl J Med 2008; 358:1229. 42. Kor DJ, Kashyap R, Weiskopf RB, et al. Fresh red blood cell
transfusion and shortterm pulmonary,
immunologic, and coagulation status: a randomized clinical trial. Am J Respir Crit Care Med 2012;
185:842. 43. Weiskopf RB, Feiner J, Toy P, et al. Fresh and stored red blood cell transfusion equivalently
induce
subclinical pulmonary gas exchange deficit in normal humans. Anesth Analg 2012; 114:511. 44. Edgren
G, KamperJørgensen M, Eloranta S, et al. Duration of red blood cell storage and survival of
transfused patients (CME). Transfusion 2010; 50:1185. 45. Silliman CC. The twoevent model of
transfusionrelated acute lung injury. Crit Care Med 2006;
34:S124. 46. Bux J, Sachs UJ. The pathogenesis of transfusionrelated acute lung injury (TRALI). Br
J Haematol
2007; 136:788. 47. Fung YL, Silliman CC. The role of neutrophils in the pathogenesis of
transfusionrelated acute lung
injury. Transfus Med Rev 2009; 23:266. 48. Bux J. Transfusionrelated acute lung injury (TRALI): a
serious adverse event of blood transfusion. Vox
Sang 2005; 89:1. 49. Sachs UJ. Pathophysiology of TRALI: current concepts. Intensive Care Med
2007; 33 Suppl 1:S3. 50. Jutzi M, Levy G, Taleghani BM. Swiss Haemovigilance Data and
Implementation of Measures for the Prevention of Transfusion Associated Acute Lung Injury (TRALI).
Transfus Med Hemother 2008; 35:98. 51. Tamarozzi MB, Soares SG, SáNunes A, et al. Comparative
analysis of the pathological events
involved in immune and nonimmune TRALI models. Vox Sang 2012; 103:309. 52. Silliman CC,
Kelher MR, Khan SY, et al. Experimental prestorage filtration removes antibodies and
decreases lipids in RBC supernatants mitigating TRALI in vivo. Blood 2014; 123:3488. 53.
Kleinman SH, Triulzi DJ, Murphy EL, et al. The Leukocyte Antibody Prevalence StudyII (LAPSII): a
retrospective cohort study of transfusionrelated acute lung injury in recipients of highplasmavolume
human leukocyte antigen antibodypositive or negative components. Transfusion 2011; 51:2078. 54.
Cooling L. Transfusionrelated acute lung injury. JAMA 2002; 288:315. 55. Win N, Ranasinghe E, Lucas
G. Transfusionrelated acute lung injury: a 5year lookback study.
Transfus Med 2002; 12:387. 56. Nicolle AL, Chapman CE, Carter V, Wallis JP. Transfusionrelated
acute lung injury caused by two
donors with antihuman leucocyte antigen class II antibodies: a lookback investigation. Transfus Med
2004; 14:225. 57. Curtis BR, Cox NJ, Sullivan MJ, et al. The neutrophil alloantigen HNA3a (5b) is
located on choline transporterlike protein 2 and appears to be encoded by an R>Q154 amino acid
substitution. Blood 2010; 115:2073. 58. Dykes A, Smallwood D, Kotsimbos T, Street A.
Transfusionrelated acute lung injury (Trali) in a patient
with a single lung transplant. Br J Haematol 2000; 109:674. 59. Middelburg RA, Van Stein D,
Zupanska B, et al. Female donors and transfusionrelated acute lung
injury: A casereferent study from the International TRALI Unisex Research Group. Transfusion 2010;
50:2447. 60. Middelburg RA, van Stein D, Atsma F, et al. Alloexposed blood donors and
transfusionrelated acute
lung injury: a casereferent study. Transfusion 2011; 51:2111. 61. Middelburg RA, van Stein D, Briët
E, van der Bom JG. The role of donor antibodies in the
pathogenesis of transfusionrelated acute lung injury: a systematic review. Transfusion 2008;
48:2167. 62. Bux J. Antibodymediated (immune) transfusionrelated acute lung injury. Vox Sang 2011;
100:122. 63. Sachs UJ. Recent insights into the mechanism of transfusionrelated acute lung injury. Curr
Opin
Hematol 2011; 18:436. 64. Sachs UJ, Hattar K, Weissmann N, et al. Antibodyinduced neutrophil
activation as a trigger for
transfusionrelated acute lung injury in an ex vivo rat lung model. Blood 2006; 107:1217.

65. Seeger W, Schneider U, Kreusler B, et al. Reproduction of transfusionrelated acute lung injury in an
ex vivo lung model. Blood 1990; 76:1438. 66. Looney MR, Nguyen JX, Hu Y, et al. Platelet
depletion and aspirin treatment protect mice in a two
event model of transfusionrelated acute lung injury. J Clin Invest 2009; 119:3450. 67. Silliman CC,
Voelkel NF, Allard JD, et al. Plasma and lipids from stored packed red blood cells cause
acute lung injury in an animal model. J Clin Invest 1998; 101:1458. 68. Kelher MR, Masuno T,
Moore EE, et al. Plasma from stored packed red blood cells and MHC class I
antibodies causes acute lung injury in a 2event in vivo rat model. Blood 2009; 113:2079. 69. Looney MR,
Su X, Van Ziffle JA, et al. Neutrophils and their Fc gamma receptors are essential in a
mouse model of transfusionrelated acute lung injury. J Clin Invest 2006; 116:1615. 70. Thompson
JS, Severson CD, Parmely MJ, et al. Pulmonary "hypersensitivity" reactions induced by
transfusion of nonHLA leukoagglutinins. N Engl J Med 1971; 284:1120. 71. Flesch BK, Neppert J.
Transfusionrelated acute lung injury caused by human leucocyte antigen class
II antibody. Br J Haematol 2002; 116:673. 72. BRITTINGHAM TE. Immunologic studies on
leukocytes. Vox Sang 1957; 2:242. 73. Nakagawa M, Toy P. Acute and transient decrease in neutrophil
count in transfusionrelated acute
lung injury: cases at one hospital. Transfusion 2004; 44:1689. 74. Marques MB, Tuncer HH, Divers
SG, et al. Acute transient leukopenia as a sign of TRALI. Am J
Hematol 2005; 80:90. 75. Dry SM, Bechard KM, Milford EL, et al. The pathology of
transfusionrelated acute lung injury. Am J
Clin Pathol 1999; 112:216. 76. Curtis BR, McFarland JG. Mechanisms of transfusionrelated acute
lung injury (TRALI): antileukocyte
antibodies. Crit Care Med 2006; 34:S118. 77. Kopko PM, Popovsky MA, MacKenzie MR, et al.
HLA class II antibodies in transfusionrelated acute
lung injury. Transfusion 2001; 41:1244. 78. Densmore TL, Goodnough LT, Ali S, et al. Prevalence
of HLA sensitization in female apheresis
donors. Transfusion 1999; 39:103. 79. Triulzi DJ, Kakaiya R, Schreiber G. Donor risk factors for
white blood cell antibodies associated with transfusionassociated acute lung injury: REDSII leukocyte
antibody prevalence study (LAPS). Transfusion 2007; 47:563. 80. Davoren A, Curtis BR, Shulman IA, et
al. TRALI due to granulocyteagglutinating human neutrophil
antigen3a (5b) alloantibodies in donor plasma: a report of 2 fatalities. Transfusion 2003; 43:641. 81. Reil
A, KellerStanislawski B, Günay S, Bux J. Specificities of leucocyte alloantibodies in transfusion
related acute lung injury and results of leucocyte antibody screening of blood donors. Vox Sang 2008;
95:313. 82. Sachs UJ, Wasel W, Bayat B, et al. Mechanism of transfusionrelated acute lung injury
induced by
HLA class II antibodies. Blood 2011; 117:669. 83. Nishimura M, Hashimoto S, Takanashi M, et al.
Role of antihuman leucocyte antigen class II
alloantibody and monocytes in development of transfusionrelated acute lung injury. Transfus Med 2007;
17:129. 84. Wakamoto S, Fujihara M, Takahashi D, et al. Enhancement of endothelial permeability by
coculture
with peripheral blood mononuclear cells in the presence of HLA Class II antibody that was associated
with transfusionrelated acute lung injury. Transfusion 2011; 51:993. 85. Silliman CC, Bjornsen AJ,
Wyman TH, et al. Plasma and lipids from stored platelets cause acute lung
injury in an animal model. Transfusion 2003; 43:633. 86. Silliman CC, Moore EE, Kelher MR, et al.
Identification of lipids that accumulate during the routine
storage of prestorage leukoreduced red blood cells and cause acute lung injury. Transfusion 2011;
51:2549. 87. Khan SY, Kelher MR, Heal JM, et al. Soluble CD40 ligand accumulates in stored blood
components,
primes neutrophils through CD40, and is a potential cofactor in the development of transfusionrelated
acute lung injury. Blood 2006; 108:2455. 88. Andrews AT, Zmijewski CM, Bowman HS, Reihart JK.
Transfusion reaction with pulmonary infiltration
associated with HLAspecific leukocyte antibodies. Am J Clin Pathol 1976; 66:483. 89. Yomtovian
R, Kline W, Press C, et al. Severe pulmonary hypersensitivity associated with passive
transfusion of a neutrophilspecific antibody. Lancet 1984; 1:244.

90. Skeate RC, Eastlund T. Distinguishing between transfusion related acute lung injury and transfusion
associated circulatory overload. Curr Opin Hematol 2007; 14:682. 91. Popovsky MA.
Transfusionassociated circulatory overload: the plot thickens. Transfusion 2009; 49:2. 92. Zhou L,
Giacherio D, Cooling L, Davenport RD. Use of Bnatriuretic peptide as a diagnostic marker in
the differential diagnosis of transfusionassociated circulatory overload. Transfusion 2005; 45:1056.
93. Tobian AA, Sokoll LJ, Tisch DJ, et al. Nterminal probrain natriuretic peptide is a useful diagnostic
marker for transfusionassociated circulatory overload. Transfusion 2008; 48:1143. 94. Li G, Daniels
CE, Kojicic M, et al. The accuracy of natriuretic peptides (brain natriuretic peptide and N
terminal probrain natriuretic) in the differentiation between transfusionrelated acute lung injury and
transfusionrelated circulatory overload in the critically ill. Transfusion 2009; 49:13. 95. Rice TW, Ware
LB, Haponik EF, et al. Vascular pedicle width in acute lung injury: correlation with
intravascular pressures and ability to discriminate fluid status. Crit Care 2011; 15:R86. 96. Ely EW, Smith
AC, Chiles C, et al. Radiologic determination of intravascular volume status using
portable, digital chest radiography: a prospective investigation in 100 patients. Crit Care Med 2001;
29:1502. 97. Gajic O, Gropper MA, Hubmayr RD. Pulmonary edema after transfusion: how to
differentiate
transfusionassociated circulatory overload from transfusionrelated acute lung injury. Crit Care Med 2006;
34:S109. 98. Popovsky MA. The Emily Cooley Lecture 2009 To breathe or not to breathethat is the
question.
Transfusion 2010. 99. National Heart, Lung, and Blood Institute Acute Respiratory Distress
Syndrome (ARDS) Clinical Trials
Network, Wheeler AP, Bernard GR, et al. Pulmonaryartery versus central venous catheter to guide
treatment of acute lung injury. N Engl J Med 2006; 354:2213. 100. ARDS Definition Task Force, Ranieri
VM, Rubenfeld GD, et al. Acute respiratory distress syndrome:
the Berlin Definition. JAMA 2012; 307:2526. 101. Wallis JP, Lubenko A, Wells AW, Chapman
CE. Single hospital experience of TRALI. Transfusion
2003; 43:1053. 102. Goldberg AD, Kor DJ. State of the art management of transfusionrelated acute
lung injury (TRALI).
Curr Pharm Des 2012; 18:3273. 103. Worsley MH, Sinclair CJ, Campanella C, et al.
Noncardiogenic pulmonary oedema after transfusion
with granulocyte antibody containing blood: treatment with extracorporeal membrane oxygenation. Br J
Anaesth 1991; 67:116. 104. Wallis JP. Transfusionrelated acute lung injury (TRALI): presentation,
epidemiology and treatment.
Intensive Care Med 2007; 33 Suppl 1:S12. 105. Levy GJ, Shabot MM, Hart ME, et al.
Transfusionassociated noncardiogenic pulmonary edema.
Report of a case and a warning regarding treatment. Transfusion 1986; 26:278. 106. Peter JV, John P,
Graham PL, et al. Corticosteroids in the prevention and treatment of acute
respiratory distress syndrome (ARDS) in adults: metaanalysis. BMJ 2008; 336:1006. 107. Tang BM,
Craig JC, Eslick GD, et al. Use of corticosteroids in acute lung injury and acute respiratory
distress syndrome: a systematic review and metaanalysis. Crit Care Med 2009; 37:1594. 108. Jeddi
R, Mansouri R, Kacem K, et al. Transfusionrelated acute lung injury (TRALI) during remission induction
course of acute myeloid leukemia: a possible role for alltransretinoicacid (ATRA)? Pathol Biol (Paris)
2009; 57:500. 109. Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids
for persistent
acute respiratory distress syndrome. N Engl J Med 2006; 354:1671. 110. O'Neal HR Jr, Koyama T,
Koehler EA, et al. Prehospital statin and aspirin use and the prevalence of
severe sepsis and acute lung injury/acute respiratory distress syndrome. Crit Care Med 2011;
39:1343. 111. Kor DJ, Erlich J, Gong MN, et al. Association of prehospitalization aspirin therapy and
acute lung
injury: results of a multicenter international observational study of atrisk patients. Crit Care Med 2011;
39:2393. 112. Nordhagen R, Conradi M, Drömtorp SM. Pulmonary reaction associated with transfusion
of plasma
containing anti5b. Vox Sang 1986; 51:102. 113. Reissman P, Manny N, Shapira SC, et al.
Transfusionrelated adult respiratory distress syndrome. Isr
J Med Sci 1993; 29:303. 114. Eastlund T, McGrath PC, Britten A, Propp R. Fatal pulmonary
transfusion reaction to plasma

containing donor HLA antibody. Vox Sang 1989; 57:63. 115. Win N, Montgomery J, Sage D, et al.
Recurrent transfusionrelated acute lung injury. Transfusion
2001; 41:1421. 116. Silliman CC, Fung YL, Ball JB, Khan SY. Transfusionrelated acute lung injury
(TRALI): current
concepts and misconceptions. Blood Rev 2009; 23:245. 117. ISBT Working Party on Granulocyte
Immunobiology, Bierling P, Bux J, et al. Recommendations of the
ISBT Working Party on Granulocyte Immunobiology for leucocyte antibody screening in the
investigation and prevention of antibodymediated transfusionrelated acute lung injury. Vox Sang 2009;
96:266. 118. Su L, Kamel H. How do we investigate and manage donors associated with a suspected case
of
transfusionrelated acute lung injury. Transfusion 2007; 47:1118. 119. Mair DC, Hirschler N,
Eastlund T. Blood donor and component management strategies to prevent
transfusionrelated acute lung injury (TRALI). Crit Care Med 2006; 34:S137. 120. Eder AF, Herron
R, Strupp A, et al. Transfusionrelated acute lung injury surveillance (20032005) and the potential impact
of the selective use of plasma from male donors in the American Red Cross. Transfusion 2007; 47:599.
121. Insunza A, Romon I, GonzalezPonte ML, et al. Implementation of a strategy to prevent TRALI in a
regional blood centre. Transfus Med 2004; 14:157. 122. Wendel S, Biagini S, Trigo F, et al.
Measures to prevent TRALI. Vox Sang 2007; 92:258. 123. Reesink HW, Lee J, Keller A, et al. Measures
to prevent transfusionrelated acute lung injury (TRALI).
Vox Sang 2012; 103:231. 124. Lucas G, Win N, Calvert A, et al. Reducing the incidence of TRALI
in the UK: the results of screening
for donor leucocyte antibodies and the development of national guidelines. Vox Sang 2012; 103:10.
125. Kleinman S, Grossman B, Kopko P. A national survey of transfusionrelated acute lung injury risk
reduction policies for platelets and plasma in the United States. Transfusion 2010; 50:1312. 126. Sachs
UJ, Kauschat D, Bein G. White blood cellreactive antibodies are undetectable in
solvent/detergent plasma. Transfusion 2005; 45:1628. 127. Riedler GF, Haycox AR, Duggan AK,
Dakin HA. Costeffectiveness of solvent/detergenttreated fresh
frozen plasma. Vox Sang 2003; 85:88. 128. Sinnott P, Bodger S, Gupta A, Brophy M. Presence of
HLA antibodies in singledonorderived fresh
frozen plasma compared with pooled, solvent detergenttreated plasma (Octaplas). Eur J Immunogenet
2004; 31:271. 129. Powers A, Stowell CP, Dzik WH, et al. Testing only donors with a prior history of
pregnancy or
transfusion is a logical and costeffective transfusionrelated acute lung injury prevention strategy.
Transfusion 2008; 48:2549. 130. Carrick DM, Norris PJ, Endres RO, et al. Establishing assay cutoffs for
HLA antibody screening of
apheresis donors. Transfusion 2011; 51:2092. 131. Triulzi DJ, Kleinman S, Kakaiya RM, et al. The
effect of previous pregnancy and transfusion on HLA
alloimmunization in blood donors: implications for a transfusionrelated acute lung injury risk reduction
strategy. Transfusion 2009; 49:1825. 132. Murphy MF, Navarrete C, Massey E. Donor screening as a
TRALI risk reduction strategy. Transfusion
2009; 49:1779. 133. Tynell E, Andersson TM, Norda R, et al. Should plasma from female donors
be avoided? A population
based cohort study of plasma recipients in Sweden from 1990 through 2002. Transfusion 2010; 50:1249.
134. Kakaiya RM, Triulzi DJ, Wright DJ, et al. Prevalence of HLA antibodies in remotely transfused or
alloexposed volunteer blood donors. Transfusion 2010; 50:1328. 135. Funk MB, Guenay S,
Lohmann A, et al. Benefit of transfusionrelated acute lung injury risk
minimization measuresGerman haemovigilance data (20062010). Vox Sang 2012; 102:317. 136. Lin Y,
Saw CL, Hannach B, Goldman M. Transfusionrelated acute lung injury prevention measures
and their impact at Canadian Blood Services. Transfusion 2012; 52:567. 137. Blumberg N, Heal
JM, Gettings KF, et al. An association between decreased cardiopulmonary
complications (transfusionrelated acute lung injury and transfusionassociated circulatory overload) and
implementation of universal leukoreduction of blood transfusions. Transfusion 2010; 50:2738. 138.
Watkins TR, Rubenfeld GD, Martin TR, et al. Effects of leukoreduced blood on acute lung injury after

trauma: a randomized controlled trial. Crit Care Med 2008; 36:1493. 139. Biffl WL, Moore EE,
Offner PJ, et al. Plasma from aged stored red blood cells delays neutrophil
apoptosis and primes for cytotoxicity: abrogation by poststorage washing but not prestorage
leukoreduction. J Trauma 2001; 50:426.
Topic 7926 Version 29.0

GRAPHICS
Diagnostic criteria for transfusionrelated acute lung injury (TRALI) and possible
TRALI
TRALI Possible TRALI
Acute lung injury
Same as for TRALI (ALI)/acute
respiratory distress syndrome (ARDS)
ALI/ARDS risk factor at time of transfusion
Acute onset (during or within six hours of transfusion) Hypoxemia*
Bilateral infiltrates on frontal chest radiograph
No evidence of circulatory overload/left atrial hypertension
No preexisting ALI/ARDS before transfusion
Δ
Must be absent Must be present
The diagnostic criteria for TRALI and possible TRALI share the following features: acute onset of hypoxemia,
bilateral infiltrates on frontal chest radiograph, and absence of circulatory overload as the primary etiology of
respiratory insufficiency. For a diagnosis of TRALI to be made, all of these features must be present. In addition,
there should be no preexisting ALI/ARDS risk factors at the time of transfusion. If ALI/ARDS risk factors are
present, the diagnostic terminology "possible TRALI" is appropriate.
PaO2: arterial oxygen tension; FiO2: fraction of inspired oxygen; SpO2: hemoglobin oxygen saturation. *
Hypoxemia is defined as PaO2/FiO2 ≤300 or SpO2 <90 percent on room air or other clinical evidence of
hypoxemia. Δ Risk factors for ALI/ARDS include the following: aspiration, toxic inhalation, pneumonia, toxic
contusion, near drowning, shock states, severe sepsis, multiple trauma, burn injury, acute pancreatitis,
cardiopulmonary bypass, or drug overdose.
Modified from: Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion related acute lung
injury: statement of a consensus panel. Transfusion 2004; 44:1774.
Graphic 64212 Version 3.0

Helpful features in distinguishing TRALI and TACO

Feature TRALI TACO
Body temperature Fever may be present Unchanged
Blood pressure Hypotension may be present Hypertension may be present
Respiratory symptoms Acute dyspnea Acute dyspnea
Neck veins Unchanged May be distended
Auscultation Rales Rales and S3 may be present
Chest radiograph Diffuse bilateral infiltrates Diffuse bilateral infiltrates
Ejection fraction Normal Decreased
PAOP Most often 18 mmHg or less Greater than 18 mmHg
Pulmonary edema fluid Exudate Transudate
Fluid balance Neutral or negative Positive
Response to diuretics Inconsistent Significant improvement
White cell count Transient leukopenia may be
present
Unchanged
BNP <250 pg/mL >1200 pg/mL
TRALI: transfusionrelated acute lung injury; TACO: transfusionassociated circulatory overload; PAOP: pulmonary
artery occlusion pressure; BNP: brain natriuretic peptide.
Modified with permission from: Skeate RC, Eastlund T. Distinguishing between transfusion related acute lung injury
and transfusion associated circulatory overload. Curr Opin Hematol 2007; 14:682. Copyright © 2007 Lippincott
Williams & Wilkins.
Graphic 86939 Version 4.0

Disclosures
Disclosures: Steven Kleinman, MD Consultant/Advisory Boards: Creative Testing Solutions [blood donor laboratory testing];
Cerus [pathogen inactivation of blood components (platelet blood system, plasma blood system)]. Daryl J Kor, MD Nothing to
disclose. Arthur J Silvergleid, MD Nothing to disclose. Scott Manaker, MD, PhD Consultant/Advisory boards: Expert witness in
workers' compensation and in medical negligence matters [General pulmonary and critical care medicine]. Equity
Ownership/Stock Options (Spouse): Johnson & Johnson; Pfizer (Numerous medications and devices). Other Financial Interest:
Director of ACCP Enterprises, a wholly owned forprofit subsidiary of ACCP [General pulmonary and critical care medicine
(Providing pulmonary and critical care medicine education to nonmembers of ACCP)]. Jennifer S Tirnauer, MD Nothing to
disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multilevel review process, and through requirements for references to be provided to support the content.
Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of
interest policy

Trali Uptodate PDF

Caricato da

Informazioni sul documento

Titolo originale

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

Trali Uptodate PDF

Caricato da

Copyright:

Formati disponibili

7/12/2015 Transfusion-related acute lung injury (TRALI)

Transfusionrelated acute lung injury (TRALI)

Helpful features in distinguishing TRALI and TACO

Potrebbero piacerti anche

Trali Uptodate PDF

Caricato da

Informazioni sul documento

Titolo originale

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

Trali Uptodate PDF

Caricato da

Copyright:

Formati disponibili

7/12/2015 Transfusion-related acute lung injury (TRALI)

Transfusion​related acute lung injury (TRALI)

Helpful features in distinguishing TRALI and TACO

Potrebbero piacerti anche

Transfusionrelated acute lung injury (TRALI)