HaematologyTier 1Disease (DEADMAN)

Transfusion-related acute lung injury

Description

Non-cardiogenic pulmonary oedema within 6 hours of transfusion
Acute hypoxaemia + bilateral infiltrates + no evidence of left atrial hypertension or circulatory overload
Hypotension is characteristic (whereas TACO gives hypertension)
Often with fever, rigors, transient leucopenia
*The commonest cause of transfusion-related death before haemovigilance-driven donor deferral; still a leading cause*

~1 in 5,000-10,000 units transfused; falling steeply since male-predominant plasma donor policies
Plasma-rich components carry the highest risk: FFP is the most commonly implicated product, then apheresis platelets, then red cells
No sex or age predilection in recipients
Higher risk in critically ill, septic, post-cardiac-surgery, massive transfusion and haematological patients

Two-hit model

First hit (recipient) - a primed pulmonary endothelium and adherent neutrophils
- Sepsis, recent surgery (especially cardiac), trauma, mechanical ventilation, chronic alcohol use, shock, active malignancy
Second hit (product) - one of:
- Immune (~80%): donor anti-HLA class I/II or anti-HNA (human neutrophil antigen) antibodies binding recipient leucocytes
  - -> neutrophil activation, aggregation in pulmonary capillaries, oxidative burst, protease release
  - -> capillary leak and protein-rich pulmonary oedema
  - *Antibodies come from the donor, and are commonest in multiparous women* - hence the shift to male plasma
- Non-immune: biologically active lipids and CD40 ligand accumulating during component storage
Rarely, recipient antibodies against donor leucocytes (reverse TRALI) - passenger leucocytes in the product

2019 consensus redefinition

TRALI type I - no ARDS risk factors present
TRALI type II - ARDS risk factors present, or existing mild ARDS that worsens
"Possible TRALI" as a category has been retired

*A clinical diagnosis of exclusion, made at the bedside.*

Criteria

Onset within 6 hours of transfusion (usually 1-2 h)
Acute hypoxaemia - PaO2/FiO2 <=300 mmHg, or SpO2 <90% on room air
Bilateral pulmonary infiltrates on CXR
No evidence of left atrial hypertension / circulatory overload as the sole explanation
No pre-existing ARDS (type I) or ARDS risk factors present with worsening (type II)

Supporting features

Hypotension (often the discriminating sign), fever, rigors
Transient leucopenia and monocytopenia in the first hours - neutrophils sequestered in the lung
Frothy, protein-rich pulmonary secretions
Normal or low BNP; normal JVP; normal echo

The distinction that matters - TRALI vs TACO

	TRALI	TACO
Blood pressure	Hypotension	Hypertension
JVP / fluid balance	Normal	Raised, positive balance
Fever	Common	Absent
WCC	Transient leucopenia	Normal
BNP/NT-proBNP	Normal	Raised
Echo	Normal LV	Elevated filling pressures
Pulmonary oedema fluid	Protein-rich (exudate)	Transudate
Response to diuretic	None - may harm	Rapid improvement
Risk group	Any; primed endothelium	Elderly, cardiac or renal failure, small body size, rapid/large volume

Other differentials

Anaphylactic transfusion reaction - earlier (minutes), urticaria, angioedema, bronchospasm
Bacterial contamination/septic transfusion reaction - high fever, rigors, shock
Aspiration, pneumonia, pulmonary embolism, transfusion-associated dyspnoea

Investigations

ABG, CXR, BNP, echocardiogram, FBE (leucopenia)
Notify the blood service - donor and recipient HLA/HNA antibody testing and cross-matching of donor antibody against recipient antigen
- Confirms the mechanism and, more importantly, allows the implicated donor to be deferred permanently**

*Supportive only. There is no specific therapy.*

A. Immediate

Stop the transfusion; keep IV access with saline
Oxygen; escalate to high-flow, CPAP or intubation as required (~70-80% need ventilatory support, ~20-40% invasive ventilation)
Lung-protective ventilation - low tidal volume (6 mL/kg predicted body weight), as for ARDS
Fluid resuscitation and vasopressors for hypotension

B. What NOT to do

*Diuretics do not help and can worsen hypotension* - the problem is capillary leak, not volume
- If the distinction from TACO is genuinely unclear, cautious diuresis with close monitoring is reasonable, but hypotension argues against it
Corticosteroids have no proven benefit
Do not give further plasma-rich components from the implicated donor

C. Reporting and prevention

Report every case to the blood service and the haemovigilance programme - this is what drives donor deferral and has reduced incidence
Implicated donors are permanently deferred from plasma and platelet donation

D. Systemic prevention (already in place in Australia)

Male-predominant (or previously untransfused, nulliparous female) plasma for FFP
Female apheresis platelet donors with a pregnancy history screened for HLA antibodies
Universal leucodepletion
*And the single most effective measure: avoid unnecessary transfusion* - particularly prophylactic FFP for mildly abnormal clotting in non-bleeding patients

E. Future transfusion

The recipient is NOT at increased risk of recurrence (the antibody was the donor's)
No special products required subsequently - unlike most other transfusion reactions

Fresh frozen plasma and apheresis platelets (plasma-rich components)
Multiparous donors - anti-HLA/anti-HNA antibodies from prior pregnancy
Recipient priming states - sepsis, cardiac surgery, massive transfusion, chronic alcohol excess, shock, mechanical ventilation, haematological malignancy
ARDS (shares the final common pathway)
TACO (the principal differential, and they can coexist)
Transfusion-associated dyspnoea, anaphylactic and septic transfusion reactions
IVIG and other plasma-derived products (rare reports)

*Usually resolves within 48-96 hours* - much faster than ARDS from other causes
CXR clears within days; most survivors have no long-term respiratory sequelae
Mortality ~5-10% (higher in critically ill and haematology patients)
A minority progress to established ARDS with prolonged ventilation

Complications

Respiratory failure requiring intubation and prolonged ICU stay
Ventilator-associated pneumonia, barotrauma
Multi-organ failure in the already critically ill
Under-recognition - frequently misattributed to TACO, pneumonia or the underlying illness, so the donor is never identified and continues to donate

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