Transfusion-related acute lung injury (TRALI)

Overview

TRALI is a non-cardiogenic acute lung injury occurring within 6 hours of blood transfusion - one of the leading causes of transfusion-related mortality in the UK. Distinguishing it from TACO is the key clinical and exam challenge.

Pathophysiology

•Donor plasma antibodies (anti-HLA class I/II or anti-HNA) react with recipient leucocytes - massive neutrophil activation in pulmonary capillaries

•Increased pulmonary capillary permeability → protein-rich alveolar flooding (non-cardiogenic; left atrial pressure is normal)

•'Two-hit' model: first hit = pre-existing inflammation (sepsis, surgery, haematological malignancy) primes neutrophils; second hit = transfusion activates them

•Most commonly associated with plasma-rich products - FFP and apheresis platelets carry the highest antibody load

Presentation

•Onset within 6 hours of transfusion (usually during or shortly after)

•Acute breathlessness, non-productive cough, hypoxia (SpO2 drop), tachypnoea, tachycardia

•Hypotension - key distinguishing feature from TACO

•Fever and rigors - due to inflammatory response

•No peripheral oedema, no raised JVP, no hypertension

🎯

TRALI causes hypotension; TACO causes hypertension. Both cause bilateral CXR infiltrates - cardiovascular findings and fluid balance are what separate them.

Investigations

•CXR - bilateral pulmonary infiltrates; normal heart size (helps differentiate from TACO)

•ABG - confirms hypoxaemia; PaO2:FiO2 <300 mmHg

•BNP/NT-proBNP - normal or minimally elevated in TRALI; significantly elevated in TACO - key discriminatory test

•FBC - may show transient leucopenia (neutrophil margination in lungs)

•Anti-leucocyte antibody testing (HLA class I/II and HNA) - donor and recipient samples; retrospective confirmation

•Echocardiography - normal LV function and filling pressures in TRALI; useful when BNP equivocal

Diagnostic criteria

•Acute onset of new/worsening respiratory symptoms

•Bilateral pulmonary infiltrates on CXR

•Hypoxaemia - SpO2 <90% on room air, or PaO2:FiO2 ratio <300 mmHg

•No evidence of pre-existing acute lung injury before transfusion

•No evidence of circulatory overload (TACO) as the primary cause

•Onset within 6 hours of completing blood component transfusion

Management

🥇 First-line

•stop the transfusion immediately - keep IV line open with normal saline

•high-flow supplemental oxygen via non-rebreather mask; titrate to SpO2 >94%

🥈 Second-line

•non-invasive ventilation (CPAP or BiPAP) if hypoxaemia not corrected with high-flow oxygen

🥉 Third-line

•invasive mechanical ventilation using lung-protective strategy (low tidal volume, as in ARDS)

•Send implicated blood unit and post-transfusion patient sample to blood bank for anti-leucocyte antibody testing

•Report via SHOT and to MHRA (Yellow Card scheme) as a serious adverse reaction

⚠️

Diuretics are contraindicated in TRALI - pulmonary oedema is driven by capillary leak, not fluid overload. Diuresis will not resolve alveolar flooding and may precipitate cardiovascular collapse. This is the opposite of TACO management.

Prevention

•Male-only plasma donation (UK NHSBT policy) - multiparous women develop HLA antibodies through pregnancy; male donors have very low HLA antibody prevalence

•Leucodepletion of all blood components - standard UK practice since 1999

•HLA antibody screening of female donors who have been pregnant - deferred from plasma donation if antibodies detected

Prognosis

•Most patients improve with supportive care within 48-96 hours; generally better prognosis than ARDS from other causes

•Implicated donor must be deferred pending investigation; permanently deferred if antibodies confirmed reactive against recipient antigens

TRALI vs TACO

TRALI vs TACO - key differentiators

Feature	TRALI	TACO
Mechanism	Non-cardiogenic (capillary leak)	Cardiogenic (fluid overload)
Blood pressure	Hypotension	Hypertension
JVP / peripheral oedema	Absent	Raised JVP, oedema
BNP/NT-proBNP	Normal / minimally elevated	Significantly elevated
CXR	Bilateral infiltrates, normal heart size	Bilateral infiltrates, cardiomegaly
Fluid balance	Not positive	Positive
Diuretics	Contraindicated - worsens hypotension	First-line treatment