Trali

TRANSFUSION-RELATED ACUTE LUNG

INJURY( TRALI)

DR VEERESH

MMC RI MYSORE

Introduction

bull Transfusion-related acute lung injury (TRALI)

represents Acute Lung Injury(ALI) after transfusion of

one or more plasma-containing blood products

developing within 6 hours of completion of transfusion

bull Though not uncommon it is difficult to prove as the cause

for the ALI as there is lack of knowledge about it

bull It has emerged as the most important cause of morbidity

and mortality resulting from blood transfusion

bull

bull Transfusion-related acute lung injury (TRALI) is a rare

complication of blood transfusion

bull The incidence reported in 1985 was 1 in 5000 U transfused But

recent studies shows that incidence is 1 in1000 to 2400 units

bull Plasma containing blood components such as whole blood

platelet concentrates fresh frozen plasma packed red cells

granulocytes cryoprecipitate and intravenous

immunoglobulin have all been implicated as a possible cause of

TRALI

Clinical features of transfusion-related acute lung injury

Dyspnoearespiratory distress requiring oxygen support Virtually all

Requiring mechanical ventilation 70

Documented hypoxemia Virtually all

Cyanosis Very common

Hypotension Majority

Fever Very common

Hypertension Unusual

DEFINITION

bull A Working Party on Definitions of Adverse Transfusion Events

was established by the European Haemovigilance Network

(EHN) This group has suggested that the following be the

minimum requirements for a clinical diagnosis of TRALI

bull 1) the occurrence of acute respiratory distress during or within 6

hrs of transfusion

bull 2) absence of signs of circulatory overload

bull 3) radiographic evidence of bilateral pulmonary infiltrates

bull Also has been defined by the Canadian Consensus Conference

Panel on TRALI and by National Heart Lung and Blood

Institute (NHLBI) Working Group on TRALI as new acute lung

injury (ALI) within six hours of a completed transfusion

bull Applying this definition TRALI is a clinical syndrome rather than

a disease with a single aetiology

Canadian Consensus Conference Proposed Criteria for

Transfusion -Related Acute Lung Injury (TRALI)

Criteria for TRALI

Acute lung injury (ALI)Acute onset Hypoxemia

In research setting

Ratio of PaO2FiO2 lt300 or

SpO2 lt90 at room air

Non research settingRatio of PaO2FiO2 lt300 or

SpO2 lt90 at room air

Other clinical evidence of hypoxia

Bilateral infiltrates on frontal chest radiograph

No evidence of left atrial hypertension (ie circulatory overload)

No preexisting AL I before transfus ion d uring or within 6 h of transfusion andNo temporal relationship to an alternative risk factor for ALI

Criteria for possible TRALI

Acute lung injury (ALI )

No preexisting ALI before transfusion

During or within 6 h of transfusion andA clear tempora l rela tionship to an alternative risk factor for ALI

The National Heart Lung and Blood Institute (NHLBI) Working

Group recognized that ALI in patients with other recognized risk

factor (such as trauma sepsis) would be difficult to classify as

TRALI and such cases would be designated as indeterminate

bull The Consensus Panel designates these indeterminate cases

as possible TRALI a category used by the Consensus Panel

for cases in which ALI is temporally related to a transfusion in

the presence of one other risk factor for ALI

bull The guidelines recommend classifying each suspected case in

one of the following 3 categories (1) TRALI(2) Possible

TRALI or (3) Not TRALI

bull Laboratory tests which strongly support but are not required for

the clinical diagnosis of TRALI include the

bull Demonstration of human leukocyte antigen (HLA) class I or class

II or

bull Neutrophil-specific antibodies in donor plasma

PATHOGENESIS

bull The exact pathogenesis of TRALI is not known thus several

theories have been proposed Two basic mechanisms have

been proposed for the pathogenesis of TRALI for

immune competent hosts

(1) single event hypothesis

(2) Two-event model

bull Other possible mechanisms - Several other explanations for

TRALI have been suggested but these are not supported by

clinical and experimental evidence

bull These include direct injury to pulmonary endothelium

bull Immune complex formation with complement activation and

bull Cytokine network activation

RISK FACTORS

Multiparous donors

Blood components platelet Concentratesgtfresh frozen

plasmagtpacked red cellsgtgranulocytesgtcryoprecipitategt

intravenous immunoglobulin

Massive transfusion

bull Stored blood products Inflammatory mediators like cytokines

and lipid soluble substances accumulate during storage of blood

products

bull Underlying clinical condition Factors such as trauma major

surgery sepsis may serve as initial priming event in the

development of TRALI (Two event hypothesis)

MANAGEMENT

Immediate Actions When Considering the

Diagnosis of Transfusion -Related Acute Lung Injury

1 Stop the transfusion immediately

2 Support the patient

3 If the patient is intubated obtain undiluted edema fluid as soon as possible

(preferably within 15 min) and simultaneous plasma for determination of total protein

concentrations

4 Obtain a complete blood count with differential and chest radiograph

5 Notify the blood bank of possible transfusion-related acute lung injury request a

different unit and quarantine other units from the same donor

6 Follow institutional policies for a trans fusion reaction workup and send blood

bank

bull A patient blood specimenbull Bags from units of blood transfused in the last 6 h

bull A copy of transfus ion record forms

bull Indicate the last unit transfused if possible

bull Results of the patient rsquos human leukocyte antigen type if available

bull For mild TRALI cases supplemental oxygen and supportive

care may be sufficient

bull For the most severe cases IV fluids mechanical or non-

invasive ventilation and invasive cardiovascular monitoring

may be required A low tidal volume strategy with low plateau

pressures should be employed when ventilating TRALI

patients just like other causes of ALIARDS

bull Extracorporeal membrane oxygenation has been used

successfully in a severe case of TRALI

bull Other less well-documented and unproven therapies (eg

diuretics corticosteroids prostaglandin E1) have also been

used

PREVENTION

bull Avoiding blood from multiparous women these women are at the

risk of producing anti-leucocyte antibodies during previous

pregnancies

bull Donors whose blood has resulted in TRALI like reaction

previously

bull Blood which has been stored for long duration long storage

results in production of anti-leucocyte antibodies

bull Not using whole blood

bull Leukoreduction can be done by ɤ - irradiation of the blood

componentor by using micro filters in the transfusion setsor by

using centrifuged blood component which has reduced leucocytes

Transfusion Associated Circulatory

Overload(TACO)

bull There is no universally agreed-upon definition for what

constitutes TACO

bull During or within several hours of transfusion If patients

develop respiratory distress orthopnea cyanosis

tachycardia and hypertension

bull Rales on auscultation

bull Some patients may have raised JVP an S3 on cardiac

auscultation or lower limb edema A chest radiograph can

reveal cardiomegaly and interstitial infiltrates

All patients with TACO may not have all these

abnormalities

Highest risk for TACO include those younger than 3 and

those older than 60 years of age particularly those with

underlying cardiac dysfunction

The pathogenesis of TACO is similar to other

causes of acute congestive heart failure an increase in

central venous pressure and pulmonary blood volume

causes an increase in hydrostatic pressure leading to fluid

extravasation into the alveolar space

Treatment of TACO starts with discontinuing any

ongoing transfusion

Respiratory distress is treated with

the degree of respiratory support needed to maintain the

patientrsquos oxygenation

Diuretics are administered to

remove excess fluid

TRALI versus TACO

With above discussion it is still difficult to

distinguishe between the TRALI and TACO

Clinical presentation

Both TRALI and TACO are clinical diagnoses and

clinical features can sometimes distinguish between them

With both patients present with respiratory distress due to

acute onset pulmonary edema

With TRALI patients often have hypotension and fever and can

have transient leukopenia

With TACO one would typically expect hypertension and a lack

of fever and leukopenia

Features sometimes seen with TACO that would not be expected

in TRALI include raised JVP an S3 heard on cardiac

auscultation and peripheral edema

Fluid balance

A careful investigation of the patientrsquos fluid balance can

sometimes provide a clue to the underlying diagnosis in patient

with excess fluid intake pre transfusion or

significant diuresis post reaction TACO should be

considered A normal fluid balance does not however rule

out TACO or rule in TRALI

Cardiac function

Evidence of a new myocardial infarct can suggest that

pulmonary edema may not be transfusion related

Patients with known preceding congenital heart disease

are at risk for TACO

Systolic dysfunction identified

on echocardiography is also suggestive of TACO

but does not rule out TRALI

Biochemical markers

Elevated levels of brain natriuretic peptide (BNP) and

n-terminal pro-brain natriuretic peptide (NT-proBNP)

are established markers for congestive heart failure

These BNP levels can be used to distinguish between

cardiogenic and non cardiogenic pulmonary edema in patients

presenting with acute respiratory failure

Comparison of the features of transfusion related acute lung

injury and transfusion associated circulatory overload

bull Feature TRALI TACO

bull Temperature Fever is present no fever

bull Blood pressure Hypotension Hypertension

bull Respiratory

symptoms Acute dyspnea Acute dyspnea

bull JVP Unchanged Can be raised

bull Auscultation Rales Rales + S3

Chest radiograph

Diffuse bilateral infiltrates Diffuse bilateral

bull infiltrates

bull

Ejection fraction Normal decreased Decreased

PA occlusion

pressure lt 18mmhg gt18mmhg

Pulmonary

edema fluid Exudate Transudate

bull Response

to diuretic Minimal Significat

improvement

bull WBC Transient leukopenia Unchanged

BNP lt200 pgml gt1200 pgml

THANK YOU

Reference

bull Goldman M Webert KE Arnold DM Freedman J Hannon J Blajchman MA

Proceedings of a consensus conference towards an understanding of TRALI Transfus

Med Rev 2005192ndash31

bull Pradeep et al TRAL-A less commonly known complication of transfusion Indian

journal of anaesthesia 2008 52(2) 126-131

bull Christopher C Silliman Daniel R Ambruso and Lynn K Boshkov Transfusion-

related acute lung injury Blood 20051052266-2273

bull Bhatia P Tulsiani KL TRALI - A Less Commonly Known Complication of Transfusion

Indian J Anaesth 200852126-31

bull Popovsky M A and Moore S B (1985) Diagnostic and pathogenetic considerations

in transfusion-related acute lung injury Transfusion 25 573ndash577 doi 101046j1537-

2995198525686071434x

bull Kleinman S Caulfield T Chan P et al Toward an understanding of transfusion-relate

acute lung injury Statement of a consensus panel Transfusion 2004 441774ndash1789

bull Silliman CC Bjornsen AJ Wyman TH et al Plasma and lipids from stored platelets

cause acute lung injury in an animal model Transfusion 200343633-40

bull Sachs UJ Recent insights into the mechanism of transfusion-related acute lung injury

Curr Opin Hematol 2011 Nov18(6)436-42