27. Transfusion-Related Acute Lung Injury

Question 1

TRALI

Answer 1

Serious and potentially fatal complication of
blood product transfusion in which a patient develops

rapid onset lung injury and noncardiogenic pulmonary edema due to activation of immune cells in the lungs.

It can be severe enough to be life-threatening, with fever, chills, and hypoxemic respiratory failure.

Because it is a clinically diagnosed syndrome, understanding of its pathophysiology and diagnostic criteria continue to evolve.
(UTD)

Acute onset resp distress following administration of Blood Products within hours
Exclusion of other possible explanations
Hypoxaemia
Pulmonary

Question 2

Pathogenesis

1

Answer 2

generally accepted theory for TRALI pathogenesis is that it occurs via a two-hit

Neutrophil sequestration and priming –

The first hit involves neutrophil sequestration and priming in the lung microvasculature,

due to recipient factors such as endothelial injury.

Priming refers to shifting of neutrophils to a state where they will respond to an otherwise innocuous or weak signal

Endothelial cells are thought to be responsible for both the

neutrophil sequestration
(through adhesion molecules)

and priming
(through cytokine release).

Generally these events are coupled and
exist prior to the transfusion,

although there may be circumstances in which they can occur as a result of the transfusion.

Question 3

Second Hit

Answer 3

The second hit is
activation of recipient neutrophils
by a factor in the blood product.

Activation is associated 
with the release from 
neutrophils of cytokines, 
reactive oxygen species, 
oxidases, 
and proteases 
that damage the pulmonary capillary endothelium. 

This damage causes inflammatory
(non-hydrostatic) pulmonary edema.

Transfused factors responsible for host neutrophil activation can include

antibodies in the blood component directed against recipient antigens, or soluble factors such as bioactive lipids that can activate neutrophils.

Donor anti-leukocyte antibodies can bind to antigens on recipient neutrophils or possibly to other cells such as monocytes or pulmonary endothelial cells;

bioactive lipids and other soluble factors in the transfused blood component can act as biologic response modifiers (BRMs); TRALI resulting from these non-antibody BRMs is sometimes referred to as non-immune TRALI

Question 4

Pathogenisis

Answer 4

ii Mechanical

Microthrombi particulates 
stored products
-filtered by pulmonary microcirculation
- vaso occlusion
- subsequent inflammation and oedema

Biologically active lipids
activtating neutrophil oxidase
- damage pulmonary vascular endothelium

Question 5

Diagnosis and management

Answer 5

Confirming presence ALI
Excluding possible other explanations

Assess presence symptoms ALI/ARDS

Increased WOB
Hypotension
Pulmonary Oedema
Pyrexia

Question 6

Other diagnosis

Answer 6

Signs elevated venous pressure
CVP / PAOP
- fluid o/l - secondary pump failure

Upper airway obstruction
?anaphylaxis

Systmeic sx of high CO
?sepsis / SIRS
Infection of blood products

Question 7

TRALI?

Answer 7

If none of aove - consider TRALI

ABG

• allow distinguish between ALI / ARDS
• Response hypoxia to FiO2

CXR b/l infiltrates

Management as for ARDS
Aim ensure O2 (aim PaO2 >8kpa)

Minimum FiO2 - minimise O2 ali

Question 8

Other Mx

Answer 8

Fluids resus
adequate Organ perfusion

Acoid worsesning ALi

Consider NIV / IPPV
optimal peep

Diagnosis
acute onset
rapid resolution

Question 9

Diagnostic crtieria

Answer 9

Acute onset (during or within 6 hours of transfusion)
Hypoxemia*
Bilateral infiltrates on frontal chest radiograph
No evidence of circulatory overload/left atrial hypertension
No pre-existing ALI/ARDS before transfusion

Hypoxemia is defined as PaO2/FiO2 ≤300 or SpO2 <90% on room air or other clinical evidence of hypoxemia.

Question 10

New TRALI definitions as proposed in 2019

TRALI 1+2

Answer 10

TRALI type I
No risk factors for ARDS and all the following criteria are met:

Acute onset
Hypoxemia
(PaO2/FiO2 ≤300 mmHg* or SpO2 <90% on room air)
Clear evidence of bilateral pulmonary edema on imaging¶

No evidence of LAHΔ or, if LAH is present, it is judged to not be the main contributor to the hypoxemia
Onset during or within 6 hours of transfusion◊
No temporal relationship to an alternative risk factor for ARDS

Question 11

TRALI 2

Answer 11

TRALI type II Risk factors for ARDS are present (but ARDS has not been diagnosed) or mild ARDS at baseline* but with respiratory status deterioration§ that is judged to be due to transfusion based on both of the following:
Findings as described in categories a and b of TRALI type I
Stable respiratory status in the 12 hours before transfusion