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Thromb Haemost. 2014 Apr 1;111(4):625-33. doi: 10.1160/TH13-09-0730. Epub 2013 Dec 12.

Targeting factor Xa and thrombin: impact on coagulation and beyond.

Author information

1
Dr. Charles Esmon, PhD, Howard Hughes Medical Institute, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA, Tel.: +1 405 271 7571, Fax: +1 405 271 2870, E-mail: esmonc@omrf.org.

Abstract

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 proteinase-activated 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

PMID:
24336942
DOI:
10.1160/TH13-09-0730
[Indexed for MEDLINE]
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