FXII – between hypercoagulation and fibrinolysis shutdown in COVID-19 (A02)

• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2010 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 114933180

The high incidence of thrombotic events, in conjunction with prolonged activated partial thromboplastin time, suggests a possible role of coagulation factor XII (FXII) in COVID-19 pathology. FXII is a serine protease that circulates in plasma as a zymogen. Following contact with damage-associated molecular patterns such as neutrophil extracellular traps, extracellular RNAs, and polyphosphates, FXII undergoes autoactivation to FXIIa. FXIIa controls thrombus formation while being dispensable for hemostasis. Given uncontrolled neutrophil activation and widespread endothelial damage in severe COVID-19, we postulate that augmented FXIIa formation causes COVID-19-associated hypercoagulability by altering clot structure and impairing fibrinolysis. To address this objective, FXII tracing in severe COVID-19 plasma and clot formation and lysis assays, in conjunction with ex vivo and in situ clot imaging, will be performed. The results of our work are expected to recognize FXII as a propagator of thrombotic events in severe COVID-19 patients and open new treatment perspectives.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 84: Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professor Dr. Holger Hackstein, since 7/2018; Professor Dr. Wolfgang Kübler, since 7/2018; Professor Dr. Klaus T. Preissner, until 6/2018; Professorin Dr. Malgorzata Wygrecka