Presented By intern Dr Khagendra

Acharya

TRANSFUSION RELATED ACUTE

LUNG INJURY(TRALI)

Definition

TRALI is defined as an acute lung injury that is

temporally related to a blood transfusion;

specifically, it occurs within the first six hours

following a transfusion.

It is typically associated with plasma components

such as platelets and Fresh Frozen Plasma,

though cases have been reported with packed

red blood cells since there is some residual

plasma in the packed cells. The blood component

transfused is not part of the case definition.

Transfusion-related acute lung injury (TRALI) is

an uncommon syndrome that is due to the

presence of leukocyte antibodies in transfused

plasma. TRALI is believed to occur in

approximately one in every 5000 transfusions.

Leukoagglutination and pooling of granulocytes in

the recipient's lungs may occur, with release of

the contents of leukocyte granules, and resulting

injury to cellular membranes, endothelial

surfaces, and potentially to lung parenchyma. In

most cases leukoagglutination results in mild

dyspnea and pulmonary infiltrates within about 6

hours of transfusion, and spontaneously resolves.

History Transfusion-related acute lung injury (TRALI) was

first reported in 1951and 1957,and findings from the initial case series were published in 1966. In 1970 and 1971, it was postulated that leukoagglutinins to HLA and non-HLA antigens were etiologic in TRALI reactions; however, it was not until 1985, with the report of a series of 36 patients,that TRALI was recognized as a distinct clinical entity.

With more aggressive transfusion support and increased recognition of this syndrome, TRALI has become a common clinical complication of transfusion. In the past 2 reporting years, it has been named the leading cause of transfusion-related death in the United States.7

Incidence The true incidence of TRALI is unknown because

of the difficulty in making the diagnosis and because of underreporting. It is estimated to occur in 1:1300 to 1:5000 transfusions of plasma-containing products.

The mortality rate from TRALI ranges from 5% to 25%.Most patients recover within 72 hours

Plasma containing blood product such as whole blood, platelet concentrates, fresh frozen plasma(FFP) , packed red cells, granulocytes, cryoprecipitate and intervenous immunoglobulin have all been implicated as a possible cause of TRALI.

Etiology and risk factors

The etiology of TRALI is currently not fully

understood. TRALI is thought to be immune

mediated.

Antibodies directed toward Human Leukocyte

Antigens (HLA) or Human Neutrophil Antigens

(HNA) have been implicated.

1. Multiparous donor- Antibodies develop through

exposure to fetal blood.

2. Blood component – platelet concentration

>FFP>packed red

cell>granulocytes>cryoprecipitate>iv

immunoglobulin.

3. Massive transfusion

4. Stored blood products- inflammatory mediators

like cytokines and lipid soluble substance

accumulate during storage of blood product.

5. Underlying clinical condition- factors such as

trauma, major surgery, sepsis.

Pathogenesis of TRALI The exact pathogenesis of TRALI is not known thus

several theories have been proposed. Two basis

mechanism have been proposed for the pathogenesis

of TRALI for immune competent hosts.

It is hypothesized that TRALI may be precipitated by

the infusion of donor antibodies directed against

recipient leukocytes. The infusion of donor anti-HLA

(human leukocyte antigens) or anti-HNA (human

neutrophil antigens) antibodies is thought to directly

cause complement activation, resulting in the influx of

neutrophils into the lung, followed by neutrophil

activation and release of cytotoxic agents, with

subsequent endothelial damage and capillary leak

An alternate hypothesis argues that TRALI is the

result of at least two independent clinical events:

the first is related to the clinical condition of the

patient (infection, cytokine administration, recent

surgery, or massive transfusion) that causes

activation of the pulmonary endothelium.

This then leads to the sequestration of primed

neutrophils to the activated pulmonary

endothelium.

The second event is the infusion of donor derived

anti-HLA or anti-HNA antibodies directed against

antigens on the neutrophil surface and/or

biological response modifiers (e.g., lipids) in the

stored blood component that activate these

adherent, functionally hyperactive neutrophils,

causing neutrophil-mediated endothelial damage

and capillary leak.

Third hypothesis suggests that high levels of

donor derived vascular endothelial growth factor

(VEGF) or antibodies to class II HLA antigens

residing on pulmonary vascular endothelium may

directly cause endothelial shape change and

fenestration.

Criteria For TRALI

Acute onset hypoxemia.

Ratio of Pao2/FiO2 <300 or SpO2 <90% at room

temperature.

Occur during or within 6 hours before transfusion.

B/L diffuse pulmonary infiltrates

No evidence of left atrial hypertension(i.e.

circulatory overload).

Clinical feature Dyspnoea/ respiratory distress requiring o2

support-virtually all. Requiring mechanical ventilation-70% Documented hypoxemia- virtually all Cyanosis-very common. Hypotension- majority. Fever-very common Clinical exam reveals respiratory distress

and pulmonary crackles may be present with no signs of congestive heart failure or volume overload.

CXR shows evidence of bilateral

pulmonary edema unassociated

with heart failure (non-cardiogenic

pulmonary edema), with bilateral

patchy infiltrates, which may rapidly

progress to complete "white out"

indistinguishable from Acute

Respiratory Distress Syndrome

(ARDS).

) Chest radiograph at the

time TRALI was recognized,

which demonstrates

extensive bilateral areas of

consolidation in the mid and

upper lobes of the lung

consistent with aspiration or

edema with a normal cardiac

silhouette, new since the

previous examination earlier

on the same day

Diagnostic feature of TRALI

Onset within 1-6 hrs of transfusion.

Acute respiratory distress.

Acute b/l pulmonary oedema (non-cardiogenic).

Severe hypoxemia.

Hypotension.

Fever.

Mild to severe clinical spectrum.

Differential diagnosis

Transfusion-related bacterial sepsis-after transfusion of contaminated peripheral red blood cells (PRBCs) or platelet concentrates manifests as fever, hypotension, and vascular collapse, which may include respiratory distress, and must be considered in patients with pulmonary insufficiency who have undergone transfusion.

anaphylactic transfusion reactions- involve respiratory distress related to bronchospasm manifested by tachypnea, wheezing, cyanosis, and severe hypotension. Facial and truncal erythema and edema are common with urticaria, characteristically involving the head, neck, and trunk. The respiratory distress from anaphylactic transfusion reactions is related to laryngeal and bronchial edema rather than to pulmonary edema, as in TRALI. These reactions occur rapidly during the transfusion of any type of protein-containing blood component and may occur after the transfusion of small volumes of blood.

Transfusion-associated circulatory overload

(TACO) -develops within minutes to hours of

transfusion as respiratory distress with

tachypnea, tachycardia, hypertension, and

cyanosis. All blood components have been

implicated in TACO, and it rapidly responds to

aggressive diuresis and ventilatory support.

Hemolytic transfusion reaction- may overlap with

TRALI, they are easily distinguished by the

presence of hemolysis.

TRALI Vs TACO

TRALI TACO

Fever

Hypotension

Acute dyspnoea

JVP unchanged

Auscultation- rales

X-Ray- diffuse b/linfiltrates

EF- normal

Pulmonary edema fluid-exudate

Response to diuretic-minimal

No fever

Hypertension

Acute dyspnoea

Can be changed

Rales + S3

Diffuse b/l infiltrates

Decreased

Transduate

Significant improvement

Immediate management of

TRALI

Stop the transfusion immediately

Support the patient

If the patient is intubated, obtaine undiluted

edema fluid as soon as possible(within 15 min)

and simultaneous plasma for determination of

total protein.

Obtain CBC with DC and chest radiography

Notify the blood bank of possible trali request a

different unit and quarantine other unit from the

same donar.

1. For mild TRALI cases Supplimental o2 and

supportive care may be sufficient.

2. For the most severe case- IV fluid, mechanical

or non invasive ventilation and invasive

cardiovascular monitoring may be required .

3. Extracorporeal membrane oxygenation has

been used successfully in a severe case of trali.

4. Others less well documented and unproven

therapies(eg. Diuretices , corticosteroids, etc )

have also been used.

5. Antibiotics – prevention of infection

Prevention of TRALI

Avoiding blood from multiparous women- these

women are at risk of producing anti-leucocyte

antibodies during previous pregnancy.

Donors whose blood has resulted in TRALI like

rxn previously.

Blood which has been stored for long duration-

long storage results in production of anti-

leucocyte antibodies.

Not using whole blood.

Leukoreduction can be done .

Leukoreduction

To remove WBCs from RBCs and platelets.

Reduce the risk of human leukocyte antigen

(HLA) alloimminization, febrile nonhaemolytic

transfusion rxn and CMV transmission in a pt who

require these precution.

LR is usually perform by filtration,although some

apheresis collection have sufficiently precise cell

seperation to minimize WBCs content.

It is also called transfusion related

immunomodulation because it prevent TRALI i.e

possible immunosupressive and pro-inflammatory

effect mediated by donor WBCs.

Thank you