2. Introduction
• Transfusion-related acute lung injury (TRALI)
represents Acute Lung Injury(ALI) after transfusion of
one or more plasma-containing blood products
developing within 6 hours of completion of transfusion.
• Though not uncommon it is difficult to prove as the cause
for the ALI as there is lack of knowledge about it.
• It has emerged as the most important cause of morbidity
and mortality resulting from blood transfusion.
• .
3. • Transfusion-related acute lung injury (TRALI) is a rare
complication of blood transfusion.
• The incidence reported in 1985 was 1 in 5000 U transfused. But
recent studies shows that incidence is 1 in1000 to 2400 units.
• Plasma containing blood components such as whole blood,
platelet concentrates , fresh frozen plasma, packed red cells,
granulocytes , cryoprecipitate and intravenous
immunoglobulin have all been implicated as a possible cause of
TRALI.
4. Clinical features of transfusion-related acute lung injury
Dyspnoea/respiratory distress requiring oxygen support Virtually all
Requiring mechanical ventilation 70%
Documented hypoxemia Virtually all
Cyanosis Very common
Hypotension Majority
Fever Very common
Hypertension Unusual
6. • A Working Party on Definitions of Adverse Transfusion Events
was established by the European Haemovigilance Network
(EHN). This group has suggested that the following be the
minimum requirements for a clinical diagnosis of TRALI:
• 1) the occurrence of acute respiratory distress during or within 6
hrs of transfusion;
• 2) absence of signs of circulatory overload;
• 3) radiographic evidence of bilateral pulmonary infiltrates.
7. • Also has been defined by the "Canadian Consensus Conference
Panel on TRALI" and by "National Heart, Lung, and Blood
Institute (NHLBI) Working Group on TRALI" as new acute lung
injury (ALI) within six hours of a completed transfusion.
• Applying this definition, TRALI is a clinical syndrome, rather than
a disease with a single aetiology .
8. Canadian Consensus Conference Proposed Criteria for
Transfusion -Related Acute Lung Injury (TRALI)
Criteria for TRALI
Acute lung injury (ALI)
Acute onset Hypoxemia
In research setting
Ratio of PaO2/FiO2 <300 or
SpO2 <90% at room air
Non research setting
Ratio of PaO2/FiO2 <300 or
SpO2 <90% at room air
Other clinical evidence of hypoxia
Bilateral infiltrates on frontal chest radiograph
No evidence of left atrial hypertension (i.e., circulatory overload)
No preexisting AL I before transfus ion d uring or within 6 h of transfusion; and
No temporal relationship to an alternative risk factor for ALI
Criteria for possible TRALI
Acute lung injury (ALI )
No preexisting ALI before transfusion
During or within 6 h of transfusion; and
A clear tempora l rela tionship to an alternative risk factor for ALI
9. The National Heart, Lung, and Blood Institute (NHLBI) Working
Group recognized that ALI in patients with other recognized risk
factor (such as trauma, sepsis) would be difficult to classify as
TRALI and such cases would be designated as "indeterminate."
• The Consensus Panel designates these "indeterminate" cases
as "possible TRALI," a category used by the Consensus Panel
for cases in which ALI is temporally related to a transfusion in
the presence of one other risk factor for ALI.
• The guidelines recommend classifying each suspected case in
one of the following 3 categories: (1) "TRALI,"(2) "Possible
TRALI," or (3) "Not TRALI".
10. • Laboratory tests which strongly support, but are not required for
the clinical diagnosis of TRALI, include the
• Demonstration of human leukocyte antigen (HLA) class I or class
II or
• Neutrophil-specific antibodies in donor plasma .
12. • The exact pathogenesis of TRALI is not known, thus several
theories have been proposed. Two basic mechanisms have
been proposed for the pathogenesis of TRALI for
immune competent hosts,
(1) single event hypothesis
(2) Two-event model
13.
14. • Other possible mechanisms - Several other explanations for
TRALI have been suggested, but these are not supported by
clinical and experimental evidence.
• These include direct injury to pulmonary endothelium,
• Immune complex formation with complement activation, and
• Cytokine network activation .
16. Multiparous donors
Blood components: platelet Concentrates>fresh frozen
plasma>packed red cells>granulocytes>cryoprecipitate>
intravenous immunoglobulin
Massive transfusion
• Stored blood products: Inflammatory mediators like cytokines
and lipid soluble substances accumulate during storage of blood
products,
• Underlying clinical condition: Factors such as trauma, major
surgery, sepsis may serve as initial priming event in the
development of TRALI (Two event hypothesis).
18. 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 trans fusion reaction workup, and send blood
bank:
• A patient blood specimen
• Bags from units of blood transfused in the last 6 h
• A copy of transfus ion record forms
• Indicate the last unit transfused if possible
• Results of the patient’s human leukocyte antigen type if available
19. • For mild TRALI cases, supplemental oxygen and supportive
care may be sufficient.
• For the most severe cases, IV fluids, mechanical or non-
invasive ventilation and invasive cardiovascular monitoring
may be required. A low tidal volume strategy with low plateau
pressures should be employed when ventilating TRALI
patients, just like other causes of ALI/ARDS.
• Extracorporeal membrane oxygenation has been used
successfully in a severe case of TRALI.
• Other, less well-documented and unproven therapies (eg.
diuretics, corticosteroids, prostaglandin E1) have also been
used.
21. • Avoiding blood from multiparous women: these women are at the
risk of producing anti-leucocyte antibodies during previous
pregnancies.
• Donors whose blood has resulted in TRALI like reaction
previously.
• Blood which has been stored for long duration: long storage
results in production of anti-leucocyte antibodies.
• Not using whole blood.
• Leukoreduction: can be done by ɤ - irradiation of the blood
component,or by using micro filters in the transfusion sets,or by
using centrifuged blood component which has reduced leucocytes.
23. • There is no universally agreed-upon definition for what
constitutes TACO .
• During or within several hours of transfusion, If patients
develop respiratory distress, orthopnea, cyanosis,
tachycardia, and hypertension.
• Rales on auscultation,
• Some patients may have raised JVP, an S3 on cardiac
auscultation, or lower limb edema. A chest radiograph can
reveal cardiomegaly and interstitial infiltrates.
All patients with TACO may not have all these
abnormalities.
24. Highest risk for TACO include those younger than 3 and
those older than 60 years of age, particularly those with
underlying cardiac dysfunction.
The pathogenesis of TACO is similar to other
causes of acute congestive heart failure: an increase in
central venous pressure and pulmonary blood volume
causes an increase in hydrostatic pressure leading to fluid
extravasation into the alveolar space
25. Treatment of TACO starts with discontinuing any
ongoing transfusion.
Respiratory distress is treated with
the degree of respiratory support needed to maintain the
patient’s oxygenation.
Diuretics are administered to
remove excess fluid.
27. With above discussion it is still difficult to
distinguishe between the TRALI and TACO.
Clinical presentation
Both TRALI and TACO are clinical diagnoses, and
clinical features can sometimes distinguish between them.
With both, patients present with respiratory distress due to
acute onset pulmonary edema.
With TRALI, patients often have hypotension and fever, and can
have transient leukopenia.
With TACO, one would typically expect hypertension and a lack
of fever and leukopenia..
28. Features sometimes seen with TACO that would not be expected
in TRALI include raised JVP , an S3 heard on cardiac
auscultation, and peripheral edema.
Fluid balance
A careful investigation of the patient’s fluid balance can
sometimes provide a clue to the underlying diagnosis in patient
with excess fluid intake pre transfusion or
significant diuresis post reaction , TACO should be
considered. A normal fluid balance does not however rule
out TACO or rule in TRALI.
29. Cardiac function
Evidence of a new myocardial infarct can suggest that
pulmonary edema may not be transfusion related.
Patients with known preceding congenital heart disease
are at risk for TACO.
Systolic dysfunction identified
on echocardiography is also suggestive of TACO ,
but does not rule out TRALI.
30. Biochemical markers
Elevated levels of brain natriuretic peptide (BNP) and
n-terminal pro-brain natriuretic peptide (NT-proBNP)
are established markers for congestive heart failure.
These BNP levels can be used to distinguish between
cardiogenic and non cardiogenic pulmonary edema in patients
presenting with acute respiratory failure.
31. Comparison of the features of transfusion related acute lung
injury and transfusion associated circulatory overload.
• Feature TRALI TACO
• Temperature Fever is present no fever
• Blood pressure Hypotension Hypertension
• Respiratory
symptoms Acute dyspnea Acute dyspnea
• JVP Unchanged Can be raised
• Auscultation Rales Rales + S3
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• Christopher C. Silliman, Daniel R. Ambruso, and Lynn K. Boshkov. Transfusion-
related acute lung injury. Blood. 2005;105:2266-2273
• Bhatia P, Tulsiani KL. TRALI - A Less Commonly Known Complication of Transfusion.
Indian J Anaesth 2008;52:126-31
• Popovsky, M. A. and Moore, S. B. (1985), Diagnostic and pathogenetic considerations
in transfusion-related acute lung injury. Transfusion, 25: 573–577. doi: 10.1046/j.1537-
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• Kleinman S, Caulfield T, Chan P, et al: Toward an understanding of transfusion-relate
acute lung injury: Statement of a consensus panel. Transfusion 2004; 44:1774–1789
• Silliman CC, Bjornsen AJ, Wyman TH, et al. Plasma and lipids from stored platelets
cause acute lung injury in an animal model. Transfusion 2003;43:633-40.
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Curr Opin Hematol. 2011 Nov;18(6):436-42
