Transfusion-related acute lung injury

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Abbreviation: TRALI


  • Leading cause of transfusion related mortality in the US – 5-8% [1][2]
  • Occurs at a rate of 0.04-0.1%, or 1/5000, transfused blood components [3][4][5][6]
    • Higher in critically ill


  • Two-hit mechanism [3][7][8]
    • Neutrophil sequestration and priming in lung microvasculature
    • Recipient neutrophil activation by factor in the blood product (i.e. antibodies in blood component directed at recipient antigens, bioactive lipids, etc.)
      • Neutrophils release cytokines, reactive oxygen species, etc. that damage pulmonary capillary endothelium
        • Leads to inflammatory pulmonary edema

Risk factors

Recipient factors[9][10][11][12]

  • Liver disease
  • Hematologic malignancy
  • Alcohol abuse
  • High peak airway pressures on mechanical ventilation
  • Current smoking
  • Positive fluid balance
  • Massive transfusion
  • Critical illness
  • Sepsis
  • Shock

Blood component factors[11]

  • Plasma or whole blood from female donor
  • Volume of HLA class II antibody reactive to recipient HLA antigen
  • Volume of transfused anti-human neutrophil antigen antibody
  • Highest risk components (though can occur with any, including pRBC)
    • Plasma
    • Apheresis platelet concentrates
    • Whole blood

Clinical Features

  • Acute onset hypoxemic respiratory failure due to non-cardiogenic pulmonary edema occurring during or shortly after transfusion
    • Majority of cases present within minutes of initiating transfusion [3]
    • Some present 1-2 hours post-transfusion and up to 6 hours after [13][14]
  • Most common signs/symptoms[15]
    • Hypoxemia
    • New pulmonary infiltrates
    • Pink frothy secretions via ETT
    • Fever
    • Hypotension
    • Cyanosis
  • Other Symptoms
    • Tachypnea
    • Tachycardia
    • Elevated peak/plateau pressures on ventilator
    • Transient drip in peripheral neutrophil count (from neutrophil sequestration in lung)

Differential Diagnosis

Transfusion Reaction Types

Acute allergic reaction


  • Clinical diagnosis - consider in any patient during/post-transfusion who develops hypoxemic respiratory insufficiency
  • Diagnostic criteria (NHLBI working group and Canadian Consensus Conference on TRALI): [13][16]

TRALI and Possible TRALI

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS)
  • Acute onset during or within 6 hours of transfusion
  • Hypoxemia (PaO2/FiO2 <300 or SpO2 <90% RA)
  • Bilateral infiltrates on CXR
  • No evidence of volume overload
  • No pre-existing ALI/ARDS before transfusion
Same as for TRALI
ALI/ARDS risk factor* at time of transfusion Absent Present
  • ALI/ARDS risk factor* - aspiration, toxic inhalation, pneumonia, pulmonary contusion, near drowning, shock, severe sepsis, multiple trauma, burn injury, acute pancreatitis, cardiopulmonary bypass, drug overdose
    • Diagnosis of "possible TRALI" (aka "transfused ARDS") made when temporal relationship to an alternative cause for ARDS exists


  • ABG
  • CXR
  • R/O other possible etiologies (i.e. CHF, TACO, anaphylaxis, sepsis, etc.)


Onset Acute, within 6hrs Often more gradual
BP Low High
Temp Febrile Normal
JVD/pedal edema Unlikely Likely
CVP/PAWP Normal Elevated
BNP Normal Elevated
Resp Dyspneic Dyspneic
CXR B/l infiltrates B/l infiltrates


  • STOP the transfusion and report to the blood bank for transfusion reaction work-up
    • Typically includes CBC, bilirubin, haptaglobin, direct Coombs test, BNP, HLA antigen typing
  • Supportive care (i.e. treat like ARDS)
    • O2 supplementation
    • NIV pressure support or mechanical ventilation
      • If mechanical ventilation required, ARDSnet guidelines for ventilator menagement
    • BP support
    • Consider diuresis only after demonstrated hemodynamic stability
      • no early empiric administration - associated with hypotension [2][17]
    • ECMO [18]
  • Additional transfusions
    • For those who recover, no increased risk for recurrent episode from other donors
      • Transfusion of needed blood products from other donors should not be withheld


  • Majority require ICU admission and mechanical ventilation [9][19]
    • Mean duration of mechanical ventilation 40 hours, upwards of 10 days [3][9][10]


See Also

External Links


  1. Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2011. Available at www.fda/gov/biologicsbloodvaccines/safetyavailability/reportaproblem/transfusiondonationfatalities/ucm302847.htm
  2. 2.0 2.1 Looney MR, et al. Transfusion-related acute lung injury: a review. Chest. 2004;126:249
  3. 3.0 3.1 3.2 3.3 Silliman CC, et al. Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. Blood. 2003;101:454
  4. Popovsky MA, et al. Diagnostic and pathogenietic considerations in transfusion-related acute lung injury. Transfusion. 1985;25:573
  5. Wallis JP. Transfusion-related acute lung injury (TRALI) - under-diagnosed and under-reported. Br J Anaesth. 2003;90:573
  6. 6.0 6.1 Rana R, et al. Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study. Transfusion. 2006;46:1478
  7. Sillman CC. The two-event model of transfusion-related acute lung injury. Crit Care Med. 2006;34:S124
  8. Bux J, et al. The pathogenesis of transfusion-related acute lung injury (TRALI). Br J Haematol. 2007;136:788
  9. 9.0 9.1 9.2 9.3 Vlaar AP, et al. Risk factors and outcome of transfusion-related acute lung injury in the critically ill: a nested case-control study. Crit Care Med. 2007;176:886
  10. 10.0 10.1 10.2 Gajic O, et al. Transfusion-related acute lung injury in the critically ill: prospective nested case-control study. Am J Respir Crit Care Med. 2007;176:886
  11. 11.0 11.1 Toy P, et al. Transfusion-related acute lung injury: incidence and risk factors. Blood. 2012;119:1757
  12. Benson AB, et al. Transfusion-related acute lung injury in ICU patients admitted with gastrointestinal bleeding. Intensive Care Med. 2010;36:1710
  13. 13.0 13.1 Kleinman S, et al. Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel. Transfusion. 2004;44:1774
  14. Sillman CC, et al. Transfusion-related acute lung injury. Blood. 2005;105:2266
  15. van Stein D, et al. Transfusion-related acute lung injury reports in the Netherlands: an observational study. Transfusion. 2010;50:213
  16. Toy P, et al. Transfusion-related acute lung injury: definition and review. Crit Care Med. 2005;33:721
  17. Levy GJ, et al. Transfusion-associated non-cardiogenic pulmonary edema. Report of a case and warning regarding treatment. Transfusion. 1986;26:278
  18. Worsley MH, et al. Non-cardiogenic pulmonary edema after transfusion with granulocyte antibody containing blood: treatment with extracorporeal membrane oxygenation. Br J Anaesth. 1991;67:116
  19. Cite error: Invalid <ref> tag; no text was provided for refs named thriteen
  20. Looney MR, et al. Prospective study on the clinical course and outcomes in transfusion-related acute lung injury. Crit Care Med. 2014;42:1676
  21. Popovsky MA, et al. Transfusion-related acute lung injury: a neglected serious complication of hemotherapy. Transfusion. 1992;32:589
  22. Sillman CC, et al. Transfusion-related acute lung injury (TRALI): current concepts and misconceptions. Blood Rev. 2009;23:245
  23. Wallis JP, et al. Single hospital experience of TRALI. Transfusion. 2003;43:1053