ABSTRACT
Thromboembolic events are frequently reported in patients infected with the SARS-CoV-2 virus. However, the exact mechanisms of thromboembolic events remain elusive. In this work, we show that immunoglobulin G (IgG) subclass in patients with COVID-19 trigger the formation of procoagulant PLTs in a Fc-gamma-RIIA (Fc{gamma}RIIA) dependent pathway leading to increased thrombus formation in vitro. Most importantly, these events were significantly inhibited via Fc{gamma}RIIA blockade as well as by the elevation of PLTs intracellular cyclic-adenosine-monophosphate (cAMP) levels by the clinical used agent Iloprost. The novel findings of Fc{gamma}RIIA mediated prothrombotic conditions in terms of procoagulant PLTs leading to higher thrombus formation as well as the successful inhibition of these events via Iloprost could be promising for the future treatment of the complex coagulopathy observed in COVID-19 disease. Key points- Fc-gamma-receptor IIA mediated PS externalization on the PLT surface triggers increased thrombus formation - Inductors of cAMP inhibit antibody-mediated thrombus formation and may have potential therapeutic advantage in COVID-19
