Abstract 13849: Enhancing Anti-thrombotic Efficacy but Reducing Hemorrhage: Comparison and Combination Use of a Novel Integrin Outside-in Signaling Inhibitor With Current Anti-platelet Drugs

Introduction and Hypothesis: Current anti-platelets drugs cause excessive bleeding. We have developed a novel anti-platelet drug, M3mP6, which selectively inhibits integrin outside-in signaling but not ligand binding to integrin αIIbβ3. Here we test the hypothesis that M3mP6 may synergistically enhance anti-thrombotic effects of current anti-platelet drugs but reduce risk of hemorrhage. Methods and Results: One time bolus injection of M3mP6 (10 uMol/kg,15 min) has superior anti-thrombotic effect compared to high doses of clopidogrel (4 mg/kg, oral, 2 hours), and very high doses of aspirin (36 mg/kg, i.p., 1 hour), using a FeCl3-induced occlusive carotid artery thrombosis model in mice. However, unlike the high doses of clopidogrel and aspirin, M3mP6 did not affect bleeding using a tail bleeding time model. We found that M3mP6 was comparable with the loading doses of ticagrelor (3 mg/kg) and cangrelor (30 μg/kg) in anti-thrombotic efficacy. However, ticagrelor or cangrelor cause dramatically increased hemo...