Blocking the EP3 receptor for PGE2 with DG-041 decreases thrombosis without impairing haemostatic competence.

Aims: Haemostasis interrupts bleeding from disrupted blood vessels by activating platelet aggregation and coagulation. A similar mechanism termed thrombosis generates obstructive thrombi inside diseased arteries. As a consequence of this similarity, current anti-thrombotic agents increase the risk of bleeding.

Vascular wall-produced prostaglandin E2 exacerbates arterial thrombosis and atherothrombosis through platelet EP3 receptors.

Prostanoids, bioactive lipids derived from arachidonic acid (AA), are important for vascular homeostasis. Among them, prostaglandin E2 (PGE2) enhances aggregation of platelets submaximally stimulated in vitro. This results from activation of EP3, one of the four PGE2 receptors, which decreases the threshold at which agonists activate platelets to aggregate.