Transfusion medicine
Transfusion reaction
Transfusion related acute lung injury (TRALI)

Topic Completed: 1 September 2011

Revised: 15 May 2019

Copyright: 2002-2019,, Inc.

PubMed Search: Transfusion related acute lung injury [title] TRALI "loattrfree full text"[sb]

Huy Phu Pham, M.D., M.P.H.
Page views in 2018: 614
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Cite this page: Pham HP Transfusion related acute lung injury (TRALI). website. Accessed June 20th, 2019.
Definition / general
  • Per FDA data from 2005 - 2009, TRALI is the leading cause of transfusion related mortality, causing 48% of deaths (Federal Drug Administration: Fatalities Reported to FDA Following Blood Collection and Transfusion - Annual Summary for Fiscal Year 2009 [Accessed 23 October 2017])
  • Incidence of TRALI is decreasing
  • Both overdiagnosed and underdiagnosed
  • Computer screening identifies more cases of posttransfusion 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 of 0.014 - 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: (Blood Center of Wisconsin Physician Services: [Accessed 23 October 2017])
    1. TRALI criteria
      • 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)
      • No preexisting ALI before transfusion
      • Symptoms occur during or within 6 hours of transfusion
      • No temporal relationship to an alternative risk factor for ALI
    2. Possible TRALI
      • Acute lung injury / ALI
      • No pre-existing ALI before transfusion
      • Symptoms occur during or within 6 hours of transfusion
      • Clear temporal relationship to an alternative risk factor for ALI
  • Not fully understood
  • Immune mechanism:
  • Nonimmune 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 nonimmune 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)
  • Diagnosis
    • Respiratory distress during or shortly after transfusion of blood products
    • By definition, no findings of circulatory overload, no pre-existing 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)
  • Case reports
    • 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
  • 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
    • 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 using only male plasma
    Risk factors
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