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Transfusion-related Acute Lung Injury Cite this Page

Min S. Cho; Pranav Modi; Sandeep Sharma.

Author Information In this Page
Last Update: May 1, 2022. Continuing Education Activity

Introduction
Continuing Education Activity Go to:
Etiology
Transfusion-related acute lung injury (TRALI) is a clinical syndrome in which there is an acute, noncardiogenic
Epidemiology
pulmonary edema associated with hypoxia that occurs during or after a transfusion. This activity reviews the
Pathophysiology
evaluation and management of transfusion-related acute lung injury and highlights the role of the interprofessional
team in managing patients with this condition. Histopathology

Objectives: History and Physical

Evaluation
Identify diagnostic criteria for transfusion-related acute lung injury.
Treatment / Management
Describe the pathophysiology of transfusion-related acute lung injury.
Differential Diagnosis
Contrast transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload Prognosis
(TACO).
Pearls and Other Issues
Review the importance of improving care coordination amongst interprofessional team members to improve Enhancing Healthcare Team Outcomes
outcomes for patients with transfusion-related acute lung injury.
Review Questions

Access free multiple choice questions on this topic. References

Introduction Go to:
Related information
Transfusion reactions are adverse events that occur after transfusing blood products such as whole blood, fresh frozen
PMC
plasma (FFP), platelets, cryoprecipitate, granulocytes, intravenous immune globulin, allogenic and autologous stem
cells, and packed red blood cells.[1] Transfusion-related acute lung injury (TRALI), is a clinical syndrome in which PubMed

there is acute, noncardiogenic pulmonary edema associated with hypoxia that occurs during or after a transfusion.[2]
It is the leading cause of death from transfusion documented by the U.S. Food and Drug Administration (FDA).
Similar articles in PubMed
Specifically, an incident of TRALI includes 1 in 5000 units of packed red blood cells, 1 in 2000 plasma-containing
An association between decreased cardiopulmonary complications
components, and 1 in 400 units of whole-blood-derived platelet concentrates. (transfusion-related acute lung injury and transfusion-associated
[Transfusion. 2010]
circulatory overload) and implementation of universal
TRALI was first reported in the 1950s but recognized as a distinctive clinical syndrome in 1983.[3] The disorder is Transfusion-related acute lung injury and pulmonary edema in
not only diagnosed clinically but is usually confirmed by radiographic findings. Diagnostic criteria for TRALI is if critically ill patients: a retrospective study. [Transfusion. 2006]

the symptoms develop during or within 6 hours of transfusion without any risk factors for developing acute lung Review Transfusion-associated circulatory overload and
injuries such as sepsis from pneumonia, aspiration, and shock.[4] Physical symptoms include fever, hypotension, and transfusion-related acute lung injury. [Blood. 2019]

tachycardia. Clinical findings include exudative bilateral infiltrates on chest radiograph, no evidence of pulmonary Review Transfusion-related acute lung injury (TRALI): a case
vascular overload, and hypoxemia of SpO2 less than 90% on room air with a ratio of the partial pressure of oxygen to report and literature review. [S D Med. 2011]

a fractional inspired oxygen concentration of less than 300 mmHg.[5][6] Possible TRALI is when there are other risk Review [Transfusion-related acute lung injury (TRALI)].
factors for acute lung injury. Delayed TRALI is when transfusion is completed after 6 to 72 hours, and it is associated [Pneumologie. 2014]

with higher mortality.[5][7] Transfusion-related circulatory overload (TACO) needs to be ruled out as it can be on See reviews...
differential diagnosis due to the similarity of pulmonary edema picture, but due to actual volume overload.[2][3][8] See all...

In the US, TRALI has to be reported to the Blood Banking services.

Recent Activity
Etiology Go to:
Turn Off Clear

True TRALI should not have any risk factors for acute lung injury according to diagnostic criteria. TRALI is caused Transfusion-related Acute Lung Injury - StatPearls
by damage to pulmonary vasculature from neutrophil-mediated in forms of human neutrophil antigen (HNA) or
human leukocyte antigen (HLA) antibodies in donor blood which bind to antigens of a recipient. Storage of blood See more...
products can accumulate proinflammatory mediators that can cause TRALI as well. A two-hit hypothesis applies in
this clinical syndrome. Neutrophil sequestration occurs in the pulmonary vasculature, and neutrophils activate to
damage the endothelial layer, causing leakage of protein and fluid into alveolar space.[9][10]

Epidemiology Go to:

Comorbidities suggest risk factors for having TRALI, mechanical ventilation, sepsis, massive transfusion, coronary
artery bypass graft, and end-stage liver disease.[3] Higher TRALI incidence was reported with plasma from female
donors because the literature found parous female donors with multiple HLA antibodies.[11] Other literature
mentioned female donor plasma has larger quantities of anti-HLA class II and HNA positive antibodies. Blood
products that have high plasma contents have been associated with an increased rate of TRALI. Critically ill patients
have a higher incidence of TRALI, not only because they receive more blood products, but they also have clinical
manifestations that activate neutrophil sequestration before the blood transfusion which places them at a higher risk of
acquiring TRALI than the general patient population.

In the US, TRALI has been responsible for at least 30% of transfusion-related deaths. While the mortality rates have
dropped over the past decade, continued awareness is key.

Pathophysiology Go to:

Due to the two-hit hypothesis, the first hit takes place by priming of neutrophils from who are already ill from shock,
sepsis, having organ damage who also had surgery or experienced a great deal of stress from trauma.[12] Increased
levels of interleukin-8, interleukin-6, and elastase-alpha 1-antitrypsin complex cause neutrophil recruitment to the
pulmonary vasculature.[5] Conformational change in beta-2 integrins allows neutrophil to adhere to pulmonary
capillaries.[13][14] The second hit comes from the transfusion itself. Antibodies and bioactive lipids stored in blood
products activate neutrophils, resulting in capillary leakage of intracellular content-releasing proteases and elastase
from the activation of NADPH which eventually oxidase, causing pulmonary edema. Another hypothesis is called the
threshold hypothesis. There is no first hit involved. TRALI can happen in healthy patients who are transfused with
plasma that has high amounts of antibodies whose neutrophil has already activated.

Histopathology Go to:

Histopathology consists of early acute lung distress syndrome (ARDS), revealing interstitial and intra-alveolar edema
and the presence of neutrophils in the interstitial and airway. Lung sections have shown numerous neutrophils in
pulmonary capillaries and small pulmonary vessels.[15]

History and Physical Go to:

Before a blood transfusion, a complete history and physical exam needs to be done to assess the patient's clinical
status. Most likely, the hemoglobin is lower than 7, or they are actively bleeding and need a red blood cell transfusion.
Abnormal coagulation studies with consumptive coagulopathy also warrant correction with FFP or cryoprecipitate
before any interventions or emergent surgery. Within 6 hours of blood transfusion for acute TRALI or 6 to 72 hours
for delayed TRALI, patients can develop body temperature of greater than 100.4 degrees Fahrenheit or 37 degrees
Celcius or hypotension along with acute dyspnea requiring more oxygen via nasal cannula, nonbreathable mask or
even mechanical ventilation depending on severity.[8][5] Patients might use accessory muscles for respiration and
appear to be in acute distress with breathing. Because this is not fluid overload or cardiogenic edema, neck veins are
not distended. Auscultation of the lungs reveals rales and sometimes diminished breath sounds due to pulmonary
edema. TRALI is almost impossible to distinguish from ARDs based on clinical presentation.

Evaluation Go to:

A chest radiograph will show bilateral pulmonary infiltrates. Clinical characteristics of TRALI include acute dyspnea,
hypoxemia, fever, hypotension, tachycardia, leukopenia, thrombocytopenia, and normal pulmonary artery occlusion
pressure due to noncardiogenic pulmonary edema.[8]

Nearly 30% of patients will have low levels of BNP and transient leucopenia.

Treatment / Management Go to:

Immediate management of TRALI is to stop the transfusion and notify the blood bank to screen the donor unit for
antileukocyte antibodies, anti-HLA or anti-neutrophil-specific antibodies.[5] Supportive measures must be taken to
improve oxygenation. Although there is no specific treatment for TRALI, low tidal volume application is feasible in
this case as TRALI's pathophysiology is similar to acute lung distress syndrome (ARDS). Best practice is prevention.
In the United Kingdom, the incidence of TRALI was substantially reduced by using plasma from male donors and
screening female donors for HLA and HNA antibodies which are strong risk factors.

Once the transfusion is stopped, gradual recovery may take 2-4 days. The chest x-ray will improve within 2-5 days.

Differential Diagnosis Go to:

When there is a transfusion reaction with acute dyspnea from respiratory distress, acute pulmonary edema with
diffuse bilateral infiltrates in the chest x-ray, transfusion-associated circulatory overload (TACO) is in the differential
diagnosis. TACO is also a clinical diagnosis with similar clinical pictures as TRALI. However, there are distinct
features that separate two syndromes. TACO can present with fever and hypotension. Even though normal fluid
balance does not rule out TACO, it can happen to patients who have high fluid intake before the transfusion. Due to
volume overload, patients with TACO can have distended neck veins and already reduced ejection fraction (EF) from
heart failure with reduced EF. Pulmonary artery occlusion pressures could be 18 mmHg or greater, secondary to
cardiogenic pulmonary edema with elevated brain natriuretic peptide. Because of cardiogenic pulmonary edema,
TACO has transudate fluids which are low in plasma proteins.[3]

Prognosis Go to:

Despite aggressive support, mortality rates of more than 12% are reported once TRALI is diagnosed. Even those who
survive have a slow recovery.

Pearls and Other Issues Go to:

TRALI can develop within 6 hours to 72 hours of blood transfusions that are rich in plasma. Despite suspected
various hypothesis, it could certainly be prevented with a careful approach in blood transfusions, especially in those
who are more vulnerable for acquiring TRALI. Due to no definitive treatment, prevention is the best key to keep
TRALI from occurring by treating underlying diseases first.

Enhancing Healthcare Team Outcomes Go to:

The diagnosis and management of TRALI is not simple and is best done with an interprofessional team that includes a
hematologist, cardiologist, pulmonologist, internist, and a specialty trained nurse experienced with the care of these
patients. TRALI can develop within 6 hours to 72 hours of blood transfusions that are rich in plasma. Despite
suspected various hypotheses, it could certainly be prevented with the careful approach in blood transfusions,
especially in those who are more vulnerable to acquire TRALI. Due to no definitive treatment, prevention is the best
key to keep TRALI from occurring by treating underlying diseases first.

Nurses who administer blood should be aware of this syndrome as it may present with shortness of breath. At the first
sign of symptoms, the blood transfusion should be discontinued, and the patient monitored in the ICU.[16] The
patient should be closely monitored for at least the next 48-96 hours, and some patients may even require mechanical
ventilation. Nurses should ensure that the patient has DVT prophylaxis and bedsore precautions.

The outcome of patients with TRALI depends on age, the number of other organs involved, the need for mechanical
ventilation, and response to treatment.

Review Questions Go to:

Access free multiple choice questions on this topic.

Comment on this article.

References Go to:

1. Suddock JT, Crookston KP. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Aug 11, 2021.
Transfusion Reactions. [PubMed]
2. Roubinian N. TACO and TRALI: biology, risk factors, and prevention strategies. Hematology Am Soc Hematol
Educ Program. 2018 Nov 30;2018(1):585-594. [PMC free article] [PubMed]
3. Friedman T, Javidroozi M, Lobel G, Shander A. Complications of Allogeneic Blood Product Administration, with
Emphasis on Transfusion-Related Acute Lung Injury and Transfusion-Associated Circulatory Overload. Adv
Anesth. 2017;35(1):159-173. [PubMed]
4. Toy P, Popovsky MA, Abraham E, Ambruso DR, Holness LG, Kopko PM, McFarland JG, Nathens AB, Silliman
CC, Stroncek D., National Heart, Lung and Blood Institute Working Group on TRALI. Transfusion-related acute
lung injury: definition and review. Crit Care Med. 2005 Apr;33(4):721-6. [PubMed]
5. Marik PE, Corwin HL. Acute lung injury following blood transfusion: expanding the definition. Crit Care Med.
2008 Nov;36(11):3080-4. [PubMed]
6. Kim KN, Kim DW, Jeong MA. The usefulness of a classification and regression tree algorithm for detecting
perioperative transfusion-related pulmonary complications. Transfusion. 2015 Nov;55(11):2582-9. [PubMed]
7. Khan H, Belsher J, Yilmaz M, Afessa B, Winters JL, Moore SB, Hubmayr RD, Gajic O. Fresh-frozen plasma and
platelet transfusions are associated with development of acute lung injury in critically ill medical patients. Chest.
2007 May;131(5):1308-14. [PubMed]
8. Skeate RC, Eastlund T. Distinguishing between transfusion related acute lung injury and transfusion associated
circulatory overload. Curr Opin Hematol. 2007 Nov;14(6):682-7. [PubMed]
9. Sachs UJ. Recent insights into the mechanism of transfusion-related acute lung injury. Curr Opin Hematol. 2011
Nov;18(6):436-42. [PubMed]
10. Popovsky MA, Abel MD, Moore SB. Transfusion-related acute lung injury associated with passive transfer of
antileukocyte antibodies. Am Rev Respir Dis. 1983 Jul;128(1):185-9. [PubMed]
11. Toy P, Gajic O, Bacchetti P, Looney MR, Gropper MA, Hubmayr R, Lowell CA, Norris PJ, Murphy EL,
Weiskopf RB, Wilson G, Koenigsberg M, Lee D, Schuller R, Wu P, Grimes B, Gandhi MJ, Winters JL, Mair D,
Hirschler N, Sanchez Rosen R, Matthay MA., TRALI Study Group. Transfusion-related acute lung injury:
incidence and risk factors. Blood. 2012 Feb 16;119(7):1757-67. [PMC free article] [PubMed]
12. Otrock ZK, Liu C, Grossman BJ. Transfusion-related acute lung injury risk mitigation: an update. Vox Sang.
2017 Nov;112(8):694-703. [PubMed]
13. Langereis JD. Neutrophil integrin affinity regulation in adhesion, migration, and bacterial clearance. Cell Adh
Migr. 2013 Nov-Dec;7(6):476-81. [PMC free article] [PubMed]
14. Rossaint J, Zarbock A. Tissue-specific neutrophil recruitment into the lung, liver, and kidney. J Innate Immun.
2013;5(4):348-57. [PMC free article] [PubMed]
15. Nossaman BD. Transfusion-Related Acute Lung Injury (TRALI): Report of 2 Cases and a Review of The
Literature. Ochsner J. 2008 Spring;8(1):32-8. [PMC free article] [PubMed]
16. Semple JW, Rebetz J, Kapur R. Transfusion-associated circulatory overload and transfusion-related acute lung
injury. Blood. 2019 Apr 25;133(17):1840-1853. [PubMed]

Copyright © 2022, StatPearls Publishing LLC.

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