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Special Symposium on the Basic Science of Hemostasis and Thrombosis

PhD Trainee
Program: Scientific Symposia
Hematology Disease Topics & Pathways:
Fundamental Science, Research, Bleeding and Clotting, Viral, hemophilia, Bacterial, platelet disorders, Diseases, immune mechanism, SARS-CoV-2/COVID-19, Infectious Diseases, thrombotic disorders, Adverse Events, Biological Processes, molecular biology, multi-systemic interactions, pathogenesis
Monday, December 12, 2022: 4:30 PM-6:05 PM
208-210 (Ernest N. Morial Convention Center)
Co-chairs:
Kellie R. Machlus, PhD, Harvard Medical School and Boston Children's Hospital , Keith B. Neeves, PhD, University of Colorado Denver and Wilbur A. Lam, MD, PhD, Emory University, Georgia Tech, Children's Healthcare of Atlanta
Disclosures:
Lam: Sanguina, Inc: Current equity holder in private company, Patents & Royalties.
Sepsis is a leading cause of infection-related hospitalization and mortality caused by a systemic inflammatory response. The multiple organ failure associated with sepsis is driven by overactivation of the immune system, coagulation pathways, and various blood cell populations. The confluence and crosstalk between these events are often referred to as thrombo-inflammation. This session will highlight new mechanisms in sepsis induced thrombo-inflammation including new roles for platelets, the contact pathway, and the endothelium that are potential therapeutic targets.

Dr. Julie Rayes will focus on novel mechanisms by which NETosis, in general, and S100A8/A9, in particular, induce the formation of procoagulant platelets through platelet adhesion receptor GPIbα with a supporting role for CD36. This immune-driven platelet activation potentiates neutrophil recruitment, amplifying thrombo-inflammation. During infection, neutrophil activation is essential for pathogen clearance through phagocytosis, degranulation, and extracellular trap formation. NETosis is associated with the release of damage-associated molecular patterns including S100A8/A9 and S100A12 promoting a prothrombotic and proinflammatory environment. Increases in S100A8/A9 and S100A12 levels are associated with thrombotic complications and higher mortality in septic patients.

Dr. Evi Stavrou will present novel insights into the contribution of coagulation factor XII (FXII) in sepsis. FXII sits at the nexus of coagulation, inflammation, innate immunity, and microbial defense systems. Several prior studies have uncovered diverse mechanisms by which FXII modulates infectious burden and host outcomes. Dr. Stavrou’s lab has identified FXII-mediated signaling networks that initiate and propagate neutrophil thromboinflammatory responses. This talk will discuss how viral- and bacterial-derived factors interact with FXII, the structural and functional modifications arising from this crosstalk and the signaling pathways they intersect, identifying potential homeostatic functions for FXII.

Dr. Robert Flaumenhaft will describe the prothrombotic transformation of the endothelium in sepsis and discuss how stimulation of endothelial-intrinsic cytoprotective pathways can reverse this prothrombotic phenotype. Endothelial function is frequently pathologically altered in the context of sepsis, resulting in maladaptive responses that endanger the host. Among these responses, the formation of microvascular thrombi, which wall off invading pathogens from accessing the circulation, can gravely threaten vital organs during systemic infection. Loss of endothelial anticoagulant properties, expression of prothrombotic membrane proteins, and exocytosis of soluble prothrombotic factors promote clot formation. Normalization of the endothelium by stimulation of cytoprotective pathways substantially reduces this prothrombotic transformation. Unlike systemic anticoagulants, antiplatelet agents and/or antifibrinolytics targeting the endothelium provide the unique opportunity to simultaneously prevent thrombosis and promote hemostasis.

If you are attending the meeting in New Orleans, following this session, please join ASH leadership and your colleagues at the ASH Networking Reception for the Hemostasis and Thrombosis Community, taking place at the down the hallway at the Ernest N Morial Convention Center in Rivergate Terrace, from 6:30 p.m. - 7:30 p.m.

Julie Rayes, PhD

Institute of Cardiovascular Science, University of Birmingham, Birmingham, United Kingdom

Evi X. Stavrou, MD

Louis Stokes Cleveland VA Medical Center, Cleveland, OH; Department of Medicine, Division of Hematology-Oncology, Case Western Reserve University School of Medicine, Cleveland, OH

Robert Flaumenhaft, MD, PhD

Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Newton, MA

Sean Quinn, PhD

Division of Hematology and the Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA

See more of: Scientific Symposia