acute transfusion lung injury "ATLI"
Transfusion-related acute lung injury
(TRALI) is a complication following
transfusion of blood products and is
potentially a life-threatening adverse event of
transfusion.
The first case of fatal pulmonary
edema following transfusion was reported in
the 1950
TRALI is a clinical syndrome
characterized by the acute onset of
respiratory distress in a patient who
received transfusion. It can present with
a variety of symptoms and signs, most
commonly worsening of respiratory
function. Patients present with
respiratory distress (dyspnea,
tachypnea), hypoxia, hypotension (less
commonly hypertension), fever,
tachycardia and cyanosis, pulmonary
edema (frothy pulmonary secretions),
and bilateral fluffy infiltrates on chest
radiograph. The majority of cases occur
during or within 1 to 2 h of transfusion.
. INTRODUCTION
Transfusion-related acute lung injury
(TRALI) is one of the most common
causes of transfusion associated major
morbidity and death.
The results from
many national haemovigillance
programs have identified TRALI as a
significant adverse event of transfusion,
and the reported mortality rates vary
from 5 to 25%. TRALI is a life-
threatening adverse event of
transfusion.
Investigators have shown that non-
cardiogenic lung edema is also an
important pulmonary complication of
transfusion. Since Barnard’s initial
description in 1951, (6) non-cardiogenic
lung edema related to transfusion has
been widely reported using various
names, including non-cardiogenic
pulmonary edema, pulmonary
hypersensitivity and severe allergic
pulmonary edema. In 1983 Popovsky et
al. (7,8) coined the term "transfusion-
related acute lung injury".
TRALI has been reported from all types
of blood components including whole
blood, red cells, aphaeresis platelets,
whole blood platelets, fresh frozen
plasma, cryoprecipitate, granulocytes,
stem cell products and even IV
immunoglobulin preparations.
According to the literature, the
incidence is 1:5000 for blood
components with subsequent
reports ranging from 1:432 for whole
blood platelets to 1:557,000 for red
cells. The most implicated are
plasma-rich components, such as
plasma and aphaeresis platelets.
TRALI is under- diagnosed and under-
reported as many clinicians are not
familiar with the syndrome.
This is
equally true for severe cases of TRALI
where transfusion may not be
considered as a possible cause and may
be regarded as acute respiratory
distress syndrome (ARDS) but also for
mild case where mechanical ventilation
is not required.
TRALI can be
misdiagnosed as TACO (Transfusion
Associated Circulatory Overload) as
occurred in the French haemovigilance
network.
Patients who are at risk for developing
TRALI are still not properly identified.
(a) Acute onset of acute lung injury (ALI)
- (b) Hypoxemia (PaO2/FiO2 (ratio of
- partial pressure of arterial O2 to the fraction
- of inspired O2) ≤300 and must be adjusted
- downward with increasing altitude
- or SpO2≤90% on room air or other
- clinical evidence)
- (c) Bilateral lung infiltrates on frontal chest
- radiograph
- (d) No evidence of left atrial hypertension
- (i.e., transfusion-associated circulatory overload)
- (e)
- Occurrence during or within 6 h after
- completion of transfusion
- (f) No temporal relationship to
- an alternative risk factor for ALI
- (g) New ALI and no other ALI risk factors
- present including aspiration, multiple
- trauma, pneumonia, cardiopulmonary
- bypass, burn injury, toxic inhalation, lung
- contusion, acute pancreatitis, drug overdose
- , near drowning, shock and sepsis
- (h) If one or more ALI risk factors are
- present, possible TRALI should be diagnosed
- (in patients with an alternative ALI risk
- factor, TRALI is still possible)
syndrome. Sometimes, a single unit of blood
or blood product is implicated in causing the
syndrome. Patients with classic TRALI
should not have other risk factors for ALI
and, thus, the transfusion is the only
identifiable cause of the respiratory failure.
Characteristics of the “classic TRALI
syndrome” are: time of onset within 2
hours (usually up to 6 hours); rapid
development; no other risk factors for
ALI except transfusion; anti-neutrophil
antibodies pathophysiology and onset
after asingle unit of blood productCharacteristics of the “delayed TRALI
syndrome” are: time of onset 6-72
hours after transfusion; slow
development of
clinical presentation; patients have
other risk factors for ALI (i.e. sepsis,
aspiration, near-drowning,
disseminated
intravascular coagulation, trauma,
pneumonia, drug overdose, fracture,
burns and cardiopulmonary bypass);
two- step
pathophysiology and common after
massive transfusion (40-57%).
pathophysiology
fully understood.
At present we know that the common
denominator is the end of the pathway which
presents with increased pulmonary capillary
permeability, and results in movement of
plasma into the alveolar space causing
pulmonary edema. Two possible theorie
s have been proposed to explain the
pathogenesis of TRALI.
The first suggests an antibody mediated
reaction after transfusion. The antibody-
mediated model postulates that the react
ion is secondary to passive transfusion of
specific donor antibodies against recipient
antigens (human leukocyte antigen (HLA)
specific, mostly HLA-A2 or anti-granulocyte
specific antibodies like human neutrophil
antigen (HNA)-1a, -1b, -3a or HLA 1) or
infusion of donor antigens (leucocytes) in
recipient who already has antibodies again
st them.
This antibody-antigen interaction can cause
complement activation, resulting in the
pulmonary sequestration and activation of
neutrophils, endothelial cell damage, and a
capillary leak syndrome in the lungs
manifesting as TRALI.
There is evidence that TRALI is more
common in recipients of blood products from
multiparous female donors who are more
likely to possess anti-HLA antibodies and
anti–neutrophil-specific antibodies.
However, in about 5-15% of cases, no
antibody is identified in either the donor or
recipient. The second is a two-event model.
The first event (first hit) is the clinical
condition of the patient resulting in
pulmonary endothelial activation an
d polimorphonuclear (PMN) sequestration,
and the second event is the transfusion of a
biologic response modifier (including anti-
granulocyte antibodies, lipids, and CD40
ligand) that activates these adherent PMNs
resulting in endothelial damage, capillary leak,
and TRALI. These two mechanisms of injury
may not be mutually exclusive and a patient
may develop TRALI through either one or
both mechanisms
prevention
All TRALI reactions should be reported to the
transfusion service. All associated donors are
tested for HLA class I and II antibodies as well
as HNA antibodies. As the transfused units
are usually not available for testing,
this
involves recalling the donors. Associated
donors may continue donating while being
investigated but only plasma for fractionation
is used. All implicated donors (i.e. donors who
are cross match positive with the patient’s
leucocytes or donors who have the cognate
antibody to HLA class I, II or neutrophil
antigens of the patient) are permanently
deferred from donation.
