Thesis defense Laura Delvasto Núñez

The tango lesson: Complement and hemolysis in the pathogenesis of thrombosis in AIHA

On 13 January 2022 (13:00) Sanquin researcher Laura Delvasto Núñez defended her thesis 'The tango lesson: Complement and hemolysis in the pathogenesis of thrombosis in AIHA' at the University of Amsterdam

Prof SS Zeerleder MD PhD
I Jongerius PhD

University of Amsterdam, Agnietenkapel (invitation only) and online

Autoimmune hemolytic anemia (AIHA) is a rare and clinically heterogeneous disorder caused by autoantibody-initiated destruction of erythrocytes, leading to anemia. Depending on the isotype of the autoantibodies, the complement system might be involved in the clearance of the erythrocytes, which can occur either in the reticuloendothelial system (extravascular hemolysis) or in circulation (intravascular hemolysis). Besides hemolytic anemia, patients with AIHA have an increased risk of life-threatening thromboembolic complications. Retrospective studies suggest that the occurrence of these complications is associated with intravascular hemolysis as a consequence of complement activation, but the underlying mechanism for thrombosis remains largely unknown. The overall aim of this thesis was to gain insight into the pathophysiology of AIHA to identify key factors driving hypercoagulability in patients. In addition, it aimed to explore complement as a potential therapeutic target. The findings of this thesis emphasize the need for the implementation of complement-directed therapy to prevent hemolysis, inflammation and eventually thrombosis in AIHA. Additionally, we identified a procoagulant role for iron ions derived from erythrocytes during hemolysis. The research suggest that by inducing alterations on membrane phospholipids, iron ions potentiate thrombin generation. Finally, this thesis describes the development of a rat model of complement-mediated chronic intravascular hemolysis to study the interplay between complement and hemolysis in coagulation activation and the development of thrombosis in vivo.