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Hematology Disease Topics & Pathways:
Bleeding and Clotting, Diseases, Treatment Considerations
Description:
Coagulation is not a linear process that ends at clot formation. Rather, coagulation is a network of ever-growing complexity with many mechanisms and pathways for regulation and feedback. The consequences of coagulation extend well beyond clot formation and into processes related to immunity, inflammation, vascular biology and regeneration. This session will highlight three examples for how bi-directional interactions from bench to bedside and back have paved the way to paradigm shifts in mechanistic insights, diagnosis, and treatment options for bleeding disorders and thrombotic complications.
Dr. Annette von Drygalski will discuss the most recent therapeutic paradigms in hemophilia. The continued unraveling of genetic and biochemical mechanisms underlying impaired blood clotting remains critical to inform the development of groundbreaking therapeutic strategies for Hemophilia A and B. Such strategies include extended half-life clotting factor preparations, non-factor-based molecules modifying hemostasis and, lastly, gene therapy. The new therapies have great potential to improve joint bleed prevention and reduce the sequelae of hemophilic arthropathy, which remains one of the most prominent aspects of clinical management in daily practice. Dr. von Drygalski will discuss pathophysiological mechanisms contributing to hemophilic arthropathy, new imaging modalities and joint outcome measures, paving the way for more targeted and individualized treatment strategies.
Dr. Daniël Verhoef will discuss the discovery and (pre)clinical development of a modified [PR1] recombinant form of coagulation factor X, called VMX-C001, which can bypass factor Xa direct oral anticoagulants (DOACs) in patients requiring immediate reversal of anticoagulation. It carries a unique 16 amino acid insertion that was derived from a snake venom factor X that makes VMX-C001 insensitive to inhibition by FXa DOACs. A single intravenous administration of VMX-C001 was shown to restore coagulation assays in animals and human volunteers on FXa-DOACs. VMX-C001 also prevented rivaroxaban induced bleeding in a primate liver injury model. VMX-C001 holds promise as an effective FXa DOAC reversal agent given its favorable half-life, short infusion time, FXa DOAC independent dosing and lack of a prothrombotic effect.
Dr. Cristina Puy will present a comprehensive exploration of coagulation factor XI dynamic interaction with diverse ligands, substrates, and endothelial cell receptors. Delving into the intricate mechanisms, Dr. Puy will elucidate factor XI pivotal role in modulating endothelial cell permeability and barrier function, shedding light on its implications in thrombotic and inflammatory conditions. This presentation will deepen our understanding of factor XI multifaceted involvement in health and disease.
Dr. Annette von Drygalski will discuss the most recent therapeutic paradigms in hemophilia. The continued unraveling of genetic and biochemical mechanisms underlying impaired blood clotting remains critical to inform the development of groundbreaking therapeutic strategies for Hemophilia A and B. Such strategies include extended half-life clotting factor preparations, non-factor-based molecules modifying hemostasis and, lastly, gene therapy. The new therapies have great potential to improve joint bleed prevention and reduce the sequelae of hemophilic arthropathy, which remains one of the most prominent aspects of clinical management in daily practice. Dr. von Drygalski will discuss pathophysiological mechanisms contributing to hemophilic arthropathy, new imaging modalities and joint outcome measures, paving the way for more targeted and individualized treatment strategies.
Dr. Daniël Verhoef will discuss the discovery and (pre)clinical development of a modified [PR1] recombinant form of coagulation factor X, called VMX-C001, which can bypass factor Xa direct oral anticoagulants (DOACs) in patients requiring immediate reversal of anticoagulation. It carries a unique 16 amino acid insertion that was derived from a snake venom factor X that makes VMX-C001 insensitive to inhibition by FXa DOACs. A single intravenous administration of VMX-C001 was shown to restore coagulation assays in animals and human volunteers on FXa-DOACs. VMX-C001 also prevented rivaroxaban induced bleeding in a primate liver injury model. VMX-C001 holds promise as an effective FXa DOAC reversal agent given its favorable half-life, short infusion time, FXa DOAC independent dosing and lack of a prothrombotic effect.
Dr. Cristina Puy will present a comprehensive exploration of coagulation factor XI dynamic interaction with diverse ligands, substrates, and endothelial cell receptors. Delving into the intricate mechanisms, Dr. Puy will elucidate factor XI pivotal role in modulating endothelial cell permeability and barrier function, shedding light on its implications in thrombotic and inflammatory conditions. This presentation will deepen our understanding of factor XI multifaceted involvement in health and disease.