08 May

PhD Defence Matthias Heinrich Busch

Supervisors: Dr. Pieter van Paassen, Em. Prof. dr. Chris P. Reutelingsperger,

Co-supervisor: Dr. Jan G.M.C. Damoiseaux

Keywords: COVID-19, Anti-neutrophil Cytoplasmic Antibody associated Vasculitis (AAV), Hypercoagulability, Inflammation

"Inflammation and Hypercoagulability in Anti-neutrophil Cytoplasmic Antibody associated Vasculitis: Lessons learned from COVID-19"

This thesis investigated the relationship between inflammation and thrombosis in two prospective cohorts of patients with COVID-19 and Anti-neutrophil Cytoplasmic antibody-associated Vasculitis (AAV). It was found that inflammation in COVID-19 is driven by complement activation and over-activation of neutrophils with neutrophil extracellular trap formation. Thrombosis was most profoundly driven by activation of the intrinsic coagulation pathway, which, in turn, can be linked to hyper-inflammation. Clinically, hypercoagulability was linked to poor clinical outcomes. A phase 2 clinical trial was conducted in collaboration with investigators of the AMC to explore the benefits of complement inhibition by vilobelimab (C5a inhibitor) in patients with severe COVID-19. Vilobelimab was safe and its use resulted in a better prognosis and fewer thrombotic events. Comparable to what was observed in COVID-19, it was found that the thrombotic risk in patients with AAV was predominantly driven by activation of the intrinsic coagulation pathway. Underlying mechanisms might also be an over-activated complement system and neutrophils. 

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