Post on 06-Apr-2018
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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
torloni.sergio@mayo.edu
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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)
TRANSFUSION RELATED ACUTE LUNG INJURY
(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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TRANSFUSION RELATED ACUTE LUNG INJURY
(T.R.A.L.I)
TRANSFUSION RELATED ACUTE LUNG INJURY
(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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TRANSFUSION RELATED ACUTE LUNG INJURY
(T.R.A.L.I)
TRANSFUSION RELATED ACUTE LUNG INJURY
(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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TRANSFUSION RELATED ACUTE LUNG INJURY
(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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TRANSFUSION RELATED ACUTE LUNG INJURY
(T.R.A.L.I)
TRANSFUSION RELATED ACUTE LUNG INJURY
(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
University ofCambridge/National Blood Service
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
SHOT Experience and UK Initiatives on TRALI preventionSHOT Experience and UK Initiatives on TRALI prevention
Lorna MWilliamson
University ofCambridge/National Blood Service
Lorna MWilliamson
University ofCambridge/National Blood Service
http://www.shotuk.org/presentations04.htmhttp://www.shotuk.org/presentations04.htm
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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
University ofCambridge/National Blood Service
http://www.shotuk.org/presentations04.htmhttp://www.shotuk.org/presentations04.htm
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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
SHOT Experience and UK Initiatives on TRALI preventionSHOT Experience and UK Initiatives on TRALI prevention
Lorna MWilliamson
University ofCambridge/National Blood Service
Lorna MWilliamson
University ofCambridge/National Blood Service
http://www.shotuk.org/presentations04.htmhttp://www.shotuk.org/presentations04.htm
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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
SHOT Experience and UK Initiatives on TRALI preventionSHOT Experience and UK Initiatives on TRALI prevention
Lorna MWilliamson
University ofCambridge/National Blood Service
Lorna MWilliamson
University ofCambridge/National Blood Service
http://www.shotuk.org/presentations04.htmhttp://www.shotuk.org/presentations04.htm
http://www.shotuk.org/presentations04.htmhttp://www.shotuk.org/presentations04.htm
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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
SHOT Experience and UK Initiatives on TRALI preventionSHOT Experience and UK Initiatives on TRALI prevention
Lorna MWilliamson
University ofCambridge/National Blood Service
Lorna MWilliamson
University ofCambridge/National Blood Service
http://www.shotuk.org/presentations04.htmhttp://www.shotuk.org/presentations04.htm
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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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THE
END
THE
END