Development of Transfusion Related Acute Lung I njury TRALI Blood transfusions while lifesaving are also associated with a risk of morbidity and mortality due to complications such as transfusionrelated acute lung injury ID: 816743
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Slide1
The Potential of
Inflammatory Responses to Contribute to the Development of Transfusion-Related Acute Lung Injury (TRALI)
Blood transfusions, while life-saving, are also associated with a risk of morbidity and mortality due to complications such as transfusion-related acute lung injury (
TRALI).1,2
Patients develop hypoxaemia and pulmonary oedema, postulated to occur via a two-insult mechanism;1
The precise underlying mechanisms remain uncertain; however, activation of both neutrophils and monocytes has been implicated in TRALI pathogenesis .
First insult - patient’s co-morbidity and inflammatory stateSecond insult - transfusion of blood products containing antibodies and biological response modifiers (BRMs), exacerbating patient’s inflammatory state leading to TRALI.3,4
Research and Development, Australian Red Cross Blood Service, Brisbane, Queensland, AustraliaSchool of Medicine, The University of Queensland, Brisbane, Queensland, Australia Faculty of Health, Queensland University of Technology, Brisbane, Queensland, AustraliaThe Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia
Annette Sultana1,2,3, Denisa Meka1,3, Melinda M Dean1,3, Gabrielle Simonova1,4, Anne-Marie Christensen1,3, Robert L Flower1,2,3, John-Paul Tung1,2,3,4
Background:
1st Insult
BRMs
and/or
Antibodies
2nd Insult
Priming and adherence
Endothelial cell damage, fluid leakage
ROS
Enzymes
Inflammatory mediators
Slide2Methods:
Side Scatter
CD45
CD16
Data Analysis (representative data)
200
pg
/mL
1000
pg
/mL
2500
pg/mL10000 pg/mL
25000 pg/mLΔ Median Fluorescence Intensity (MFI)
Change in MFI compared tomatched control Statistical Significancedetermined at P < 0.05 using one-way ANOVA with Bonferroni post hoc test
MIP-1β5-HETE concentrations
In Vitro
Transfusion Model
Slide3Results:
IL-8
IL-12
IP-10
MIP-1
α
MIP-1
β
TNF-
α
Without LPS
IL-8
IL-6
IL-12
NS
NS
NS
NS
NS
NS
NS
NS
NS
IL-8
MIP-1
β
IL-8
MCP-1
MIP-1
α
TNF-
α
MIP-1
β
*
MCP-1*
MIP-1
α
IL-8*
IL-8
IL-6
IL-8
5-HETE
15-HETE
12-HETE
rIL-8
sCD40L
Anti-HLA-II
5-HETE
15-HETE
12-HETE
rIL-8
sCD40L
Anti-HLA-II
IL-6
IP-10
IL-8
MCP-1
IL-1
β
MIP-1
α
MIP-1
β
TNF-
α
IL-8
IL-1
α
MIP-1
β
IP-10
IL-1
α
MCP-1
MIP-1
α
MIP-1
β
IL-8
MIP-1
α
NS
NS
MIP-1
α
IL-6
IP-10
IL-1
β
MIP-1
α
TNF-α
TNF-αMIP-1β
TNF-αMIP-1β
IL-1α
IL-1αIL-6
IL-8IL-1α
IL-8IL-6
MCP-1
LPS
Decrease cf. no stimuli; NS = not significant; *changed cytokine and chemokine production; -- to be completed
Monocyte
Neutrophil
Over-all
Exposure to 12-HETE, rIL-8 or sCD40L: neutrophil and monocyte cytokine and chemokine production were reducedExposure to 5-HETE: changed neutrophil MCP-1 and monocyte MIP-1β productionExposure to 15-HETE: changed monocyte IL-8 production and reduced neutrophil cytokine and chemokine production
Neutrophil
Exposure to
12-HETE, 15-HETE, rIL-8, sCD40L or
anti-HLA-II: increased neutrophil cytokine and chemokine production
Exposure to 12-HETE or rIL-8: increased monocyte
cytokine and chemokine production
Exposure to
sCD40L:
reduced monocyte
cytokine and chemokine productionExposure to 12-HETE or anti-HLA-II antibody: increased overall cytokine and chemokine responseExposure to 15-HETE, rIL-8 or sCD40L: reduced overall cytokine and chemokine response
--
Monocyte
Overall
Decrease
cf. no stimuli; increase cf. LPS only; NS = not significant; *changed cytokine and chemokine production; -- to be completed
--
Slide4Summary:
Australian governments fund the Australian Red Cross Blood Service to provide blood, blood products and services to the Australian community
Acknowledgements:
In this
in vitro
transfusion model exposure of whole blood to
BRMs and an antibody:Reduced recipient cytokine and chemokine responses in the absence of LPS.Modulated the underlying inflammatory state (i.e. with LPS).
In vitro models useful in understanding contributions of various mediators to outcomes post-transfusionImproved understanding of TRALI provides evidence for development of strategies to reduce the risk of TRALI and improve blood transfusion safety.
References:1.Kleinman et al. (2004) Toward an understanding of TRALI: statement of consensus. Transfusion 44 (12); 1774-17892. Bolton-Maggs et al. (2013). Serious Hazards of Transfusion (SHOT) haemovigilance and progress is improving transfusion safety. British Journal of Haematology
163 (3); 303-314. 3. Silliman et al. (2011) Identification of lipids that accumulate during routine storage of prestorage leukoreduced red blood cells and cause ALI. Transfusion 51 (12); 2549-2554.4.Toy et al. (2012). Transfusion-related acute lung injury: incidence and risk factors. Blood 119 (7); 1757-1767.
Australian Red Cross Blood Service:
Research and Development team