josé a. páramo servicio de hematología clínica universidad
TRANSCRIPT
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José A. PáramoServicio de Hematología
Clínica Universidad de Navarra
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Outline
• Hemostasis and thromboinflammation
• Immunothrombosis- a double edged sword: immune defense vs damage of the host
• Leukocytes as inciters of thrombosis beyond microbian protection
• NETs and vascular pathologies
• NETs and liver disease
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Gaertner F. Sem Immunol 2016
The hemostatic system in vivo
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Kapoor S. Thromb Res 2018
Thrombogenesis
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Thromboinflammation: an important pathogenic process linked to a diverse range of human diseases
Jackson SP. Blood 2019
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Venous thrombosis as an inflammatory process
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Proinflammatory and prothrombotic function of inflamed endothelial cells
Jackson SP. Blood 2019
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Regulation of immune cell function by platelets
Ribeiro LS. Front Immunol 2019
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Brinkmann V. Science 2004
First description of the generation of NETs
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Engelmann B, Nat Rev Immunol 2013
Retention of pathogens by immunothrombosis:Recognition, containment and destruction
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Composition of NETs
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Engelmann B, Nat Rev Immunol 2013
Immunothrombosis
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Neutrophils as prominent drivers of vascular inflammation
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Mozzini C. Int Emerg J 2017
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Gould TJ. Arterioscler Thromb Vasc Biol 2014
Nucleosomes and DNA in sepsis
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Diaz JA.J Vasc Surg Venous Lymphat Disord 2013
DNA and nucleosomes in patients with DVT
van Montfoort ML. ATVB 2012
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NETs and thrombosis
Martinod K, Blood 2014
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Acute Ischemic Stroke
Stroke is a leading cause ofdeath and long-termdisability worldwide
Only two options available• Pharmacological thrombolysis with
tPA• Endovascular thrombectomy
Large Vessel Occlusion
(LVO)
Histological analysis of the thrombus
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LVOn = 45
Clinical datao Revascularizationo Neurological Scaleso Mortality 90 days
Data Integration & Analysis
New biomarkers
New pharmacological targets
Immunohistochemical analysiso NETs (NE & Citrullinated H3)o TAFIo MMP-10o FXIII
NETs and thrombosis in stroke patients
Navarro M. ISTH 2019
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LVO patients characteristics n = 45Age 70.13 ± 10.89
Sex (women) 25 (47.2)HTA 27 (60)
Glucose 121.38 ± 33.82NIHSS basal 16.74 ± 5.17
NIHSS 90 days 3.46 ± 5.49mRs basal 0.52 ± 0.77
mRs 90 days 3.15 ± 2.09Mortality 90 days 12 (26.1)
Complete Recanalization(TICI 2b or 3) 37 (82.2)
Quantitative variables: Mean ± SDCategorical variables: n (%)
Navarro M. ISTH 2019
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Citrullinated H3
NETs
Spearman
R = 0.333
p = 0.028
NE
Complete Recanalization
NE (%)
NO YES
Citrullinated H3 (%)
NO YES
Navarro M. ISTH 2019
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*
Mortality 90 days*p= 0.032
NO YES
NE (%) Citrullinated H3 (%)
NO YES
NETs
Spearman
R = 0.333
p = 0.028
NECitrullinated H3
Navarro M. ISTH 2019
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The implication of NETs in numerous pathophysiological conditions
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NETs and liver disease
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Liver Transplantation 2018; 24:1716
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Bukong TN. J Hepatol 2018
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: role of complement
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NETosis, coagulation and complement: a triangular relationship
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Therapeutic modulation of coagulation processes in sepsis
Jackson SP. Blood 2019
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Neutrophil Extracellular Traps: A New Therapeutic Target?
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