Work

OC 62.1 Differential Suppression of Arterial Versus Venous Thrombosis but Preserved Hemostasis in Mice Expressing Fibrinogen that Cannot Support Fibrin Formation

Year: 2023

Type: article

Abstract: Background: Elevated circulating fibrinogen correlates with increased risk for both cardiovascular and venous thromboembolic diseases.In vitro studies show that formation of a highly dense fibrin matrix is a major determinant of clot structure and stability.However, the precise contribution of fibrin matrix to occlusive arterial and venous thrombus formation in vivo remains largely undefined.Aims: Determine the contribution of fibrinogen versus fibrin to arterial thrombosis, venous thrombosis, and hemostatic potential in vivo.Methods: Arterial and venous thrombotic challenges as well as hemostatic tests were performed in wildtype (FgaWT) and FgaEK mice that express normal levels of fibrinogen "locked" in the monomeric form.Results: In a model arterial thrombosis, a 10% FeCl3 injury to the carotid artery resulted in similar times to occlusion between FgaWT/WT, FgaWT/ EK and FgaEK/EK mice, while Fga-/-mice were completely protected.However, when injured with 5% FeCl3, FgaEK/EK mice were partially protected from occlusion but had increased embolic events.These results suggest that fibrinogen can contribute to arterial thrombus formation independent of fibrin formation.Consistently, fibrinogen-dependent platelet aggregation and intraplatelet fibrinogen content in FgaWT/WT, FgaWT/

Source: Research and Practice in Thrombosis and Haemostasis

DOI: 10.1016/j.rpth.2023.100314