Abstract Number: OC 72.5
Meeting: ISTH 2022 Congress
Theme: Hemostatic Systems in Cancer, Inflammation and Immunity » Platelets and Infection
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with an increased risk of venous and arterial thrombosis but the underlying mechanism if still unclear.
Aims: The study would identify a mechanism implicated in platelet activation and thrombus growth during SARS-CoV-2 infection.
Methods: We performed a cross-sectional analysis of platelet function in 30 SARS-CoV-2 and 20 healthy subjects (HS) by measuring Nox2-derived oxidative stress and thromboxane (Tx) B2 and investigated if administration of monoclonal antibodies against the Spike(S) protein of SARS-CoV-2 affects platelet activation. Furthermore, we investigated in vitro if the Spike(S) protein of SARS-CoV-2 or plasma from SARS-CoV-2 enhanced platelet activation.
Results: Ex vivo studies showed enhanced platelet Nox2-derived oxidative stress and TxB2 biosynthesis and under laminar flow platelet-dependent thrombus growth in SARS-CoV-2 compared to controls; both effects were lowered by Nox2 and Toll-like receptor 4(TLR4) inhibitors. Two hours after administration of monoclonal antibodies a significant inhibition of platelet activation was observed in SARS-CoV-2 patients compared to untreated ones. In vitro study showed that S protein functionally interacts with platelet TLR4, and a docking simulation analysis suggested that TLR4 binds to S protein via three receptor-binding domains; furthermore, in platelets from SARS-CoV-2 S protein co-immunoprecipitated with TLR4. Plasma from SARS-CoV-2 patients incubated with normal platelets enhanced platelet activation and Nox2-related oxidative stress, an effect blunted by TNF-alpha inhibitor; this effect was recapitulated by an in vitro study documenting that TNF-alpha alone promoted platelet activation and amplified the platelet response to S protein via p47phox up-regulation.
Conclusion(s): The study identifies two TLR4-dependent and independent pathways promoting platelet-dependent thrombus growth and suggests inhibition of TLR4 or p47phox as a tool to counteract thrombosis in SARS-CoV-2.
To cite this abstract in AMA style:
Cammisotto V, Carnevale R, Bartimoccia S, Nocella C, Bufano M, Castellani V, Loffredo L, Sciarretta S, Coluccia A, Silvestri R, Ceccarelli G, Oliva A, Venditti M, Pugliese F, Mastroianni C, Turriziani O, Pignatelli P, Violi F. Toll-Like Receptor 4-Dependent and Independent platelet-dependent thrombosis in SARS-CoV-2 Infection [abstract]. https://abstracts.isth.org/abstract/toll-like-receptor-4-dependent-and-independent-platelet-dependent-thrombosis-in-sars-cov-2-infection/. Accessed April 25, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/toll-like-receptor-4-dependent-and-independent-platelet-dependent-thrombosis-in-sars-cov-2-infection/