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Transfusion medicine

Tranfusion reaction

Transfusion related acute lung injury (TRALI)

Reviewer: Huy Phu Pham, M.D. (see Reviewers page)
Revised: 5 November 2011, last major update September 2011
Copyright: (c) 2007-2011, PathologyOutlines.com, Inc.


● Per FDA data from 2005–2009, TRALI is the leading cause of transfusion-related mortality, causing 48% of deaths (link)
● Incidence of TRALI is decreasing
● Both overdiagnosed and underdiagnosed
● Computer screening identifies more cases of post-transfusion hypoxemia than are reported voluntarily (Am J Clin Pathol 2005;124:601)
● Mostly a clinical diagnosis
● TRALI has been reported following transfusion of all blood products
● Estimated incidence between 0.014% to 0.08% per blood product transfused
● For pRBC, incidence estimated at 1 per 5000 units
● Occurs most commonly with products containing > 60 mL plasma

Criteria for TRALI diagnosis: (link)
1. TRALI criteria
       a. ALI (Acute lung injury)
       ● Acute onset
       ● Hypoxemia-research Setting: PaO2/FiO2< 300 or SPO2 90% on room air
       ● Nonresearch setting: PzO2/FiO2 < 300 or SPO2 < 90% on room air or other clinical evidence of hypoxemia
       ● Bilateral infiltrates on frontal CXR
       ● No evidence of left atrial hypertension (i.e., circulatory overload)
       b. No preexisting ALI before transfusion
       c. Symptoms occur during or within 6 hrs of transfusion
       d. No temporal relationship to an alternative risk factor for ALI
2. Possible TRALI
       a. Acute lung injury / ALI
       b. No preexisting ALI before transfusion
       c. Symptoms occur during or within 6 hrs of transfusion
       d. Clear temporal relationship to an alternative risk factor for ALI

Clinical manifestation

● Varies from mild to life threatening
● Sudden onset of respiratory distress within 6 hours of transfusion
● Fever, hypotension, tachycardia
● Physical exam should NOT show any sign of fluid overload


● Not fully understood

Immune mechanism
● Passive transfer of HLA or neutrophil antibodies from donor to blood product recipient --> leukoagglutination in the pulmonary vasculature --> complement activation --> alveolar damage --> increase in permeability of pulmonary circulation --> pulmonary edema (Hematology Am Soc Hematol Educ Program 2006;497, Am J Clin Pathol 1999;112:216)

Non-immune mechanism
● Transfusion of other elements, including biologically active lipids that accumulate during the storage --> alveolar damage --> increase in permeability of pulmonary circulation --> pulmonary edema
● Both immune and non-immune mechanisms likely work through a “two-hit” mechanism
● First hit: patient’s underlying condition primes the lung’s endothelium and leukocytes
● Second hit: transfusion of HLA or neutrophil antibodies or biologically active lipid --> pulmonary edema
● Granulocytes accumulate within pulmonary vasculature and extravasate into alveoli (Am J Clin Pathol 1999;112:216)


● Respiratory distress during or shortly after transfusion of blood products
● By definition, no findings of circulatory overload, no preexisting acute lung injury or ARDS
● CXR shows bilateral infiltrate without cardiomegaly – important in helping to make the diagnosis
● If intubation is required, then frothy pink secretions might be seen
● Need to distinguish TRALI from other cause of ARDS, such as transfusion-associated circulatory overload (TACO), bacterial contamination, allergic reaction, ARDS, pulmonary embolism, pulmonary hemorrhage
● TRALI does not respond to diuretics (TACO does)

No typical laboratory findings associated with TRALI:
● Leukopenia, neutropenia, and monocytopenia have been reported
● Testing for lymphocyte and granulocyte antibodies is not required for diagnosis and is not predictive (Vox Sang 2007;93:70, Vox Sang 2007;92:247)


● Stop the transfusion
● Report the transfusion to transfusion medicine division to start the investigation
● Supportive management only
● Mechanical ventilation may be needed in severe cases
● Most patients improve within 48–96 hours
● Mortality is 5–10%

TRALI investigation:
● Very important
● Patients with a history of TRALI should not receive any blood products from the implicated donors
● Hospital should notify blood center following a potential case of TRALI
● Investigate pregnancy, transfusion or transplantation history of the donor
● Determine if donor has anti-HLA or anti-neutrophil antibodies; if yes, then patient is also tested to see whether an antigen-antibody interaction could be implicated


● Defer donors confirmed to be implicated in TRALI
● In 2003, UK began to use only male plasma
● In 2006, the AABB recommended that hospitals and blood centers implement TRALI mitigation strategies, such as use of male-only plasma

Risk factors

● Allogeneic red blood cell transfusion is an independent risk factor for ARDS in the intensive care unit population; follows a dose-response relationship (Crit Care 2007;11:R63)
● Transfusions of plasma-rich blood products, FFP and platelets may have higher risk of ARDS than RBC transfusions (Chest 2007;131:1308)
● Restrictive transfusion policies reduce late onset ARDS in trauma patients (J Trauma 2007;63:1)
● Plasma from female donors (Transfusion 2007;47:599)

Underlying disease of the patients:
● Critically ill patients (Crit Care Med 2007;35:1645), sepsis, chronic alcohol abuse
● Possibly presence of donor antigranulocyte or HLA class II antibodies (Am J Respir Crit Care Med 2007;176:886), increasing number of units of whole blood transfused (Am J Clin Pathol 2007;128:128)

Case reports

● Transfusions between mother and daughter (Am J Clin Pathol 2004;121:590)
● 2 cases in children (Transfus Med 2006;16:343)
● 67 year old man with transfusion for iron deficiency anemia (CMAJ 2007;177:149), recurrence 2 years later (Transfus Med 2007;17:192)

End of Transfusion Medicine > Tranfusion reaction > Transfusion related acute lung injury (TRALI)

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