TRALI - TUCSON

8/3/2019 TRALI - TUCSON

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TRANSFUSION RELATED ACUTE

LUNG INJURY

TRANSFUSION RELATED ACUTE

LUNG INJURYA. Sergio Torloni MD

Assistant Medical Director

United Blood Services

Scottsdale AZ

A. Sergio Torloni MD

Assistant Medical Director

United Blood Services

Scottsdale AZ

Medical Director

Transfusion Services / Stem Cell Collection

Therapeutic Apheresis

Mayo Clinic Hospital

Phoenix AZ

[email protected]


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What is T.R.A.L.I ?What is T.R.A.L.I ?

Severe respiratory compromise during transfusion.

- severe hypoxemia + non-cardiogenic pulmonary edema

Usually within 2 hours of tx (may be upto 4-6 hours)

TRALI IS A DIAGNOSIS OF EXCLUSION !

Severe respiratory compromise during transfusion.

- severe hypoxemia + non-cardiogenic pulmonary edema

Usually within 2 hours of tx (may be upto 4-6 hours)

TRALI IS A DIAGNOSIS OF EXCLUSION !

A SEVERE REACTION TO TRANSFUSION OF BLOOD PRODUCTSA SEVERE REACTION TO TRANSFUSION OF BLOOD PRODUCTS


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TRALI: What is it ?TRALI: What is it ?Acute respiratory distress occurring 1 2 hours after transfusion

of plasma containing blood products

Acute respiratory distress occurring 1 2 hours after transfusion

of plasma containing blood products

Symptoms %

Respiratory Distress 76

Hypotension 15

Hypertension 15

Symptoms %

Respiratory Distress 76

Hypotension 15

Hypertension 15

N=46*

*Popovsky & Haley, Immunohematology, 2000; 16** Popovsky & Moore, Transfusion, 1985

Incidence : 1 in 5000 tx (Mayo Clinic Study)**

Grossly Under diagnosed !


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TRANSFUSION RELATED ACUTE LUNG INJURY

(T.R.A.L.I)


(T.R.A.L.I)

Male / Female ratio = 1:1

Age : No age preference

Male / Female ratio = 1:1

Age : No age preference

Incidence: 0.02% of all units or 0.16% of all transfused patients*Incidence: 0.02% of all units or 0.16% of all transfused patients*

Very Likely Under diagnosedVery Likely Under diagnosed

AKA : Allergic Pulmonary Edema

Pulmonary Hypersensitivity reaction

AKA : Allergic Pulmonary Edema

Pulmonary Hypersensitivity reaction

Popovsky & Moore, Transfusion 25:573-7, 1985


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TRALI: Common SymptomsTRALI: Common Symptoms

Acute respiratory distress

Hypoxemia

Acute pulmonary edema

Fever ( 1 - 2 C elevation)

Pulmonary edema usually resolves within 96 hours

6 10% of cases result in death

Acute respiratory distress

Hypoxemia

Acute pulmonary edema

Fever ( 1 - 2 C elevation)

Pulmonary edema usually resolves within 96 hours

6 10% of cases result in death

Likely Mechanism is Immune mediated

Other mechanisms may exist (Lipid Mediator PAF like substance that primes leukocytes)

Second Hit Theory (Leukocytes already primed by previous injury i.e. hypoxia, sepsis, cytokine tx

Likely Mechanism is Immune mediated

Other mechanisms may exist (Lipid Mediator PAF like substance that primes leukocytes)

Second Hit Theory (Leukocytes already primed by previous injury i.e. hypoxia, sepsis, cytokine tx


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(T.R.A.L.I)


(T.R.A.L.I)

Differential DxDifferential Dx

Pulmonary embolism

Circulatory overload Shock

Bacterial Contamination (Sepsis)

Hemolytic Transfusion Reaction Anaphylaxis

Pulmonary embolism

Circulatory overload Shock

Bacterial Contamination (Sepsis)

Hemolytic Transfusion Reaction Anaphylaxis

Incidence : 1 in 5000 tx (Mayo Clinic Study)*

Grossly Under diagnosed !

*Popovsky & Moore, Transfusion 1985


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(T.R.A.L.I)


(T.R.A.L.I)

Causes:Causes:

Pre-formed anti white cell antibodies in donor plasma

Donor is usually a multiparous female

Pre-formed anti white cell antibodies in donor plasma

Donor is usually a multiparous female

Anti-HLA ( A, B, DR)

Anti Neutrophil (NA-1, NA-2, NB, 5b)

Sometimes, no antibody is demonstrated

Anti-HLA ( A, B, DR)

Anti Neutrophil (NA-1, NA-2, NB, 5b)

Sometimes, no antibody is demonstrated

2) Two Strikes theory

1)


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Anti Neutrophil antibodies: **

3% during pregnancy

7.7% female donors

78% of granulocyte recipients

Anti Neutrophil antibodies: **

3% during pregnancy

7.7% female donors

78% of granulocyte recipients

TRALI Mechanisms: Maternal Sensitization to Fetal AntigensTRALI Mechanisms: Maternal Sensitization to Fetal Antigens

Anti HLA antibodies*

1st pregnancy : 7.8%

2nd pregnancy: 14.6%

3rd pregnancy: 28.3%

Anti HLA antibodies*

1st pregnancy : 7.8%

2nd pregnancy: 14.6%

3rd pregnancy: 28.3%

* Densmore et al. Transfusion 1999;39:103-6

** Stroncek et al. Transfusion 1996;36: 1009-15


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When Transfusing Blood ,What else are we transfusing ?When Transfusing Blood ,What else are we transfusing ?

RBC


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Preformed anti HLA or Anti Neutrophil Antibodies Bind to Recipients WBCPreformed anti HLA or Anti Neutrophil Antibodies Bind to Recipients WBC

1) Donor has Antibodies to Recipients WBC1) Donor has Antibodies to Recipients WBC


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Preformed anti HLA or Anti Neutrophil Antibodies Bind to Donors WBCPreformed anti HLA or Anti Neutrophil Antibodies Bind to Donors WBC

2) Recipient has Antibodies to Donors WBC2) Recipient has Antibodies to Donors WBC

Recipient WBCRecipient WBC

Donor WBCDonor WBC


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IL1

IL6

TNF IL8

Leukocyte ActivationLeukocyte Activation

Vascular permeability


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CytokinesCytokines

IL 1IL 1FF:: Causes fever by production of PG ECauses fever by production of PG E22IL 1IL 1FF:: Causes fever by production of PG ECauses fever by production of PG E22

TNFTNF

IL6IL6

IL1IL1

TNFTNF

IL6IL6

IL1IL1

mediators of inflammationmediators of inflammationmediators of inflammationmediators of inflammation


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Antibody Binds to GranulocytesAntibody Binds to Granulocytes


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Alveoloar Space

Alveolar Capillary

Alveolar Capillary

Terminal Bronchiole

Activated Neutrophils Adhere to Pulmonary Endothelium


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Alveolar Space

Alveolar membrane

Endothelium

Activated Neutrophils Release ProteasesActivated Neutrophils Release Proteases


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Endothelium

Increased Vascular PermeabilityIncreased Vascular Permeability


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Sequence of Events in TRALISequence of Events in TRALIWBC Anti WBC interaction

WBC are trapped in the pulmonary vasculature

WBCs Release Cytokines and Enzymes

Pulmonary Vascular Injury

Increased Vascular permeability

Pulmonary Edema

WBC Anti WBC interaction

WBC are trapped in the pulmonary vasculature

WBCs Release Cytokines and Enzymes

Pulmonary Vascular Injury

Increased Vascular permeability

Pulmonary Edema


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(T.R.A.L.I)


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TRALI : Origin of AntibodiesTRALI : Origin of Antibodies

Most Common:

Donor has antibody against target antigen in donor WBC

Less Common:

Recipient has antibody to target antigen in donor WBC

Most Common:

Donor has antibody against target antigen in donor WBC

Less Common:

Recipient has antibody to target antigen in donor WBC

Who has antibodies to whom ?Who has antibodies to whom ?


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TRALI Mechanisms: Two ModelsTRALI Mechanisms: Two Models

Donor AntibodiesDonor Antibodies

Antibody activates WBC

Complement is Activated

C5 causes WBC aggregation

Pulmonary Leukostasis

Leukocyte degranulation

Antibody activates WBC

Complement is Activated

C5 causes WBC aggregation

Pulmonary Leukostasis

Leukocyte degranulation

Two HitTwo Hit

WBCs Primed by Cytokines or LPS

Lipid Mediators present in transfused plasma

WBC are activated in Pulmonary Vasculature

Respiratory Burst & Protease Release

WBCs Primed by Cytokines or LPS

Lipid Mediators present in transfused plasma

WBC are activated in Pulmonary Vasculature

Respiratory Burst & Protease Release

PULMONARY EDEMA


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TRALI : Mechanisms Involved

1. WBC, Lipids , Protein mediators

2. HLA activation of WBC

3. Activated WBC produce Cytokines

4. PAF production (loss of cell to cell contact)

5. Endothelial cells metabolize LTA4 to LTC4 ( Vascular permeability)

6. Inflammation WBC dwell time in lungs

7. TNF endothelial cell expression of ICAM


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(T.R.A.L.I)


(T.R.A.L.I)

Clinical Outcome*

Oxygen Support 36 100%

Mechanical Ventilation 26 72%

Pulmonary infiltrates 35 97%

Deaths 2 5%

Long time sequalae 0

*Popovsky & Moore, Transfusion 1985

Popovsky & Haley , Transfusion 2000

SHOT** study: 18 cases (6 deaths!)

**Serious Hazards of Transfusion reporting system


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How Important is TRALI ?How Important is TRALI ?

CBER : Fatality rate is greater than 10 %CBER : Fatality rate is greater than 10 %

SHOT*: 70 confirmed cases of TRALI have resulted in 18 deaths &SHOT*: 70 confirmed cases of TRALI have resulted in 18 deaths &

49 cases of major morbidity49 cases of major morbidity

CBER : Fatality rate is greater than 10 %CBER : Fatality rate is greater than 10 %

SHOT*: 70 confirmed cases of TRALI have resulted in 18 deaths &SHOT*: 70 confirmed cases of TRALI have resulted in 18 deaths &

49 cases of major morbidity49 cases of major morbidity

*Serious Hazards of Transfusion


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TRALI cases by diagnosis (n = 139)

35%

38%

4%5%

9%

9%

Haem-onc

Surgery

Acute h'age

Correctn coag

Sepsis

Plasma exchange

SHOT Experience and UK Initiatives on TRALI preventionSHOT Experience and UK Initiatives on TRALI prevention

Lorna MWilliamson

University ofCambridge/National Blood Service

Lorna MWilliamson


http://www.shotuk.org/presentations04.htmhttp://www.shotuk.org/presentations04.htm


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Timing of onset of symptoms (n = 108)

63%

25%

7%

5%

D/


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Components implicated

(n = 139)

Components implicated

(n = 139)

FFP/cryosupernate 45

Red cells 34

Platelets 27

Whole blood 2

Cryoprecipitate 2 Other 4 (SDFFP, I/V IgG,MBFFP, buffy coat)

Unassignable 25

FFP/cryosupernate 45

Red cells 34

Platelets 27

Whole blood 2

Cryoprecipitate 2 Other 4 (SDFFP, I/V IgG,MBFFP, buffy coat)

Unassignable 25


Lorna MWilliamson


Lorna MWilliamson




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Components implicated/total issues

(n = 139)

Components implicated/total issues

(n = 139)

Risk from high plasma components was 5-8 times

higher than from low plasma components.

HIGH PLASMA (300 MLS)

FFP /CSP 45/ 2.6 million = 1: 58,000

Platelets 27/ 1.7 million = 1: 63,000

LOW PLASMA (30 MLS)

Cryoppt 2/ 0.6 million = 1: 300,000

Red cells 34/17.8 million = 1: 523,000

SHOT Experience and UK Initiatives on TRALI prevention

Lorna MWilliamson




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Probability of TRALI according

to component implicated

Probability of TRALI according

to component implicated

0

2

4

6

8

10

12

14

1618

FFP Platelets Red

cells

High

Low


Lorna MWilliamson


Lorna MWilliamson




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Positive serological investigations in

donors 1998-2003 (n = 71)

Positive serological investigations in

donors 1998-2003 (n = 71)

PositiveXmatch

18

Cognateantigen

18

Antibodiesonly

14

HLA antibodies (cIass I orII)

50

Both HLA and

granulocyte reactive5

PositiveXmatch

6

Cognateantigen

2

Antibodiesonly

8

Granulocyte

reactive16

71 cases


Lorna MWilliamson


Lorna MWilliamson





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TRALI cases reported to SHOT

(n = 155)

0

10

20

30

40

50

1996 1997 1998 1999 2000 2001 2003

12

months

15

months


Lorna MWilliamson


Lorna MWilliamson




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TRALI :What CanWe Do to Prevent it ?TRALI :What CanWe Do to Prevent it ?

Leukocyte antibody screen of all donors ?

Collect plasma only from low risk donors

Collect plasma only from male donors ?

SERIOUS IMPACT ON PLASMA SUPPLY !

Leukocyte antibody screen of all donors ?

Collect plasma only from low risk donors

Collect plasma only from male donors ?

SERIOUS IMPACT ON PLASMA SUPPLY !


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Incidence US & European DataIncidence US & European Data

European Data (SHOT* study)

70 cases per 17 million blood components

European Data (SHOT* study)

70 cases per 17 million blood components

US Data (Popovsky et al)

- 0.02% of all blood components transfused

- 0.16% of all patients transfused (1 in 625)

US Data (Popovsky et al)

- 0.02% of all blood components transfused

- 0.16% of all patients transfused (1 in 625)

*Serious Hazards of Transfusion


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Products Containing PlasmaProducts Containing Plasma

PRBC or WB FFP Platelets Cryoprecipitate

Can Cause TRALIBone Marrow Granulocytes


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TRALITRALI

Transfusion Related DeathsTransfusion Related Deaths

1) Hemolytic Transfusion Reaction

2) Long time sequellae of Hepatitis C

3) TRALI

1) Hemolytic Transfusion Reaction

2) Long time sequellae of Hepatitis C

3) TRALI

Sazama K,. Reports of 355 Transfusion Associated Deaths

Transfusion 30: 583-590 (1990)

Sazama K,. Reports of 355 Transfusion Associated Deaths

Transfusion 30: 583-590 (1990)


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My First Case of TRALI 58 yr old dwarf

Pneumectomy for TB in late 40s

Transfusion for refractory anemia

Sudden SOB, Hypotention

Transferred to ICU Intubated

CXR complete pulmonary white out 4 days on the respirator

Recovered fully !

58 yr old dwarf

Pneumectomy for TB in late 40s

Transfusion for refractory anemia

Sudden SOB, Hypotention

Transferred to ICU Intubated

CXR complete pulmonary white out 4 days on the respirator

Recovered fully !


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What to do when TRALI is suspectedWhat to do when TRALI is suspected

Blood Bank is notified

Medical Director evaluates case

UBS form needs to be filled out

Samples are drawn for lab work

Blood Bank is notified

Medical Director evaluates case

UBS form needs to be filled out

Samples are drawn for lab work

What happens at the lab ?

EDTA/Citrate; + ClotSerological Workup for HLA class I & II antibodies

Serological Workup for Anti Neutrophil antibodies

What happens at the lab ?

EDTA/Citrate; + ClotSerological Workup for HLA class I & II antibodies

Serological Workup for Anti Neutrophil antibodies


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Serological InvestigationSerological Investigation Indirect:

GCLT: Granulocyte Chemoluminescent Test

GIFT: Granulocyte Immunoflulorescence Test LIFT: Lymphocyte Immunofluorescense Test

Indirect:

GCLT: Granulocyte Chemoluminescent Test

GIFT: Granulocyte Immunoflulorescence Test LIFT: Lymphocyte Immunofluorescense Test

MAIGA: Monoclonal antibody immobilization of Granulocyte AntigenMAIPA: Monoclonal Antibody immobilization of Platelet Antigens

ELISA: Enzyme Lynked Immunosorbent Assay

MAIGA: Monoclonal antibody immobilization of Granulocyte AntigenMAIPA: Monoclonal Antibody immobilization of Platelet Antigens

ELISA: Enzyme Lynked Immunosorbent Assay


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TRALI: Role of the Medical DirectorTRALI: Role of the Medical Director

Educate Clinicians

Evaluate patients who have respiratory distress during Tx.

Go through the list of differential diagnosis

Discuss the case with the clinicians

Initiate TRALI work-up when appropriate.

Educate Clinicians

Evaluate patients who have respiratory distress during Tx.

Go through the list of differential diagnosis

Discuss the case with the clinicians

Initiate TRALI work-up when appropriate.


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Are Clinicians Aware of TRALI ?Are Clinicians Aware of TRALI ?

1 Donor linked to a TRALI fatality

Chart review of recipients of previous donations

- 50 patients had received components from same donor- 13 patients had reactions related to tx

- 7 reactions were reported to Blood Bank (46.7%)

1 Donor linked to a TRALI fatality

Chart review of recipients of previous donations

- 50 patients had received components from same donor- 13 patients had reactions related to tx

- 7 reactions were reported to Blood Bank (46.7%)


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TRALI : When in Doubt Dont despairTRALI : When in Doubt Dont despair

Call one of the UBS Medical Directors for Assistance !


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TRALI - TUCSON