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Thromb Haemost 2014; 111(04): 625-633
DOI: 10.1160/TH13-09-0730
Review Article
Schattauer GmbH

Targeting factor Xa and thrombin: impact on coagulation and beyond

Charles T. Esmon
1   Howard Hughes Medical Institute, Coagulation Biology Laboratory, Oklahoma Medical Research Foundation, and Departments of Pathology and Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
› Author Affiliations Financial support: The author received no direct financial support. Editorial support was funded by Bayer HealthCare Pharmaceuticals and Janssen Scientific Affairs, LLC.
Further Information

Publication History

Received: 04 September 2013

Accepted after minor revision: 07 November 2013

Publication Date:
29 November 2017 (online)

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Summary

Great advances have been made in recent years in understanding the haemostatic system and the molecular and cellular basis of thrombus formation. Although directly targeting factor Xa or thrombin (factor IIa) for effective anticoagulation is now well established, evidence has emerged suggesting that factor Xa and thrombin are involved in other physiological and pathophysiological cellular processes, including inflammation. These non-haemostatic activities of factor Xa and thrombin are predominantly mediated via the activation of proteinaseactivated receptors. Studies have indicated a potential role of coagulation proteins (including factor Xa and thrombin) in the progression of disease conditions such as atherothrombosis. Preclinical studies have provided evidence for the effects of direct factor Xa or direct thrombin inhibition beyond anticoagulation, including anti-inflammatory activities and atherosclerotic plaque stabilisation. In this article, the non-haemostatic activities of factor Xa and thrombin and the effects of direct inhibition of these coagulation factors on these activities are summarised. In addition, the potential roles of factor Xa and thrombin in atherosclerosis and atherothrombosis are explored and the cardiovascular profiles of rivaroxaban, apixaban and dabigatran etexilate observed in phase III clinical studies are discussed.

Keywords

Atherothrombosis - coagulation factors - proteinase-activated receptors (PAR) - thrombin
 

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