Abstract Number: PB1465
Meeting: ISTH 2020 Congress
Theme: Platelet Disorders and von Willebrand Disease » Platelet Antagonists and Novel Therapeutics
Background: The combination of aspirin with a P2Y12 receptor (P2Y12R) antagonist has been shown to prevent major adverse cardiac events and is standard of care for patients with acute coronary syndrome. P2Y12R antagonism, and thus suppression of ADP-induced intra-platelet signaling, was shown to destabilize the interaction between GPIIb-IIIa and fibrinogen in vitro.
Aims: To investigate the effect of the P2Y12R antagonist, selatogrel, on stability of platelet-thrombi in experimental thrombosis models in vivo.
Methods: Experimental thrombosis was evaluated using Folt’s model in guinea pigs and with real-time intravital microscopy in mice.
Results: Selatogrel administered subcutaneously stopped cyclic flow variations within 10 minutes after injection, confirming a fast onset of action. During ongoing thrombosis, selatogrel reversed blood flow to baseline levels, suggesting that existing platelet-thrombi were reduced in size. Quantification of laser-induced thrombus formation in mice using intravital microscopy demonstrated that selatogrel induced the dissolution of newly formed platelet thrombi. In a separate set of experiments, platelet thrombi were given time to consolidate for 30 minutes in vivo. Fibrin formation was not suppressed during thrombus consolidation. Infusion of selatogrel dissolved the consolidated platelet thrombi, confirming that P2Y12R-mediated intra-platelet signaling is essential for maintenance of the interaction between fibrin and the GPIIb-IIIa receptor. In addition, while selatogrel dissolved platelet thrombi, dissolution was never complete; mural platelet aggregates, functioning as hemostatic seals, were resistant in the presence of selatogrel.
Conclusions: Data presented here uncovered a novel role of P2Y12R in stabilization of consolidated platelet-thrombi. In addition, selatogrel dissolved platelet thrombi with no effect on hemostatic seals, which are critical to limit blood loss following vessel damage. Our data suggest that administration of selatogrel to patients with acute coronary syndrome might not only prevent further thrombosis but also reduce the size of pre-existing platelet-thrombi.
To cite this abstract in AMA style:
Crescence L, Kramberg M, Baumann M, Rey M, Panicot-Dubois L, Dubois C, Riederer MA. Selatogrel, a Potent P2Y12 Receptor Antagonist, Dissolves Pre-Formed Platelet-thrombi in vivo [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/selatogrel-a-potent-p2y12-receptor-antagonist-dissolves-pre-formed-platelet-thrombi-in-vivo/. Accessed January 27, 2022.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/selatogrel-a-potent-p2y12-receptor-antagonist-dissolves-pre-formed-platelet-thrombi-in-vivo/