This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lentz, S. R. Search for Related Content PubMed PubMed Citation Articles by Lentz, S. R. Related Collections Animal models of human disease Pathophysiology Genetically altered mice Arterial thrombosis Coagulation and fibronolysis Related Article

(Circulation. 2005;111:1733-1734.)
© 2005 American Heart Association, Inc.

Editorial

Another Lesson From the Factor V Leiden Mouse

Thrombin Generation Drives Arterial Disease

Steven R. Lentz, MD, PhD

From the Department of Internal Medicine, University of Iowa, Iowa City, Iowa, and the Veterans Affairs Medical Center, Iowa City, Iowa.

Correspondence to Steven R. Lentz, MD, PhD, Department of Internal Medicine, C32 GH, University of Iowa, Iowa City, IA 52242. E-mail steven-lentz@uiowa.edu

Key Words: Editorials • thrombin • thrombophilia • activated protein C resistance • factor V Leiden

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The discovery of activated protein C (APC) resistance by Dahlbäck in 1993¹ was a milestone in thrombophilia research that led to major advances in our understanding of the biochemistry, genetics, and clinical manifestations of hypercoagulability. APC resistance was quickly demonstrated to be caused by a single point mutation (1691GA) in the coding region of the factor V gene.² This mutation, factor V Leiden, is now known to be the most prevalent risk factor for venous thromboembolism (VTE) in people of European descent, occurring in 3% to 15% of the general population in Europe and North America.³ These observations ushered in a new era in the clinical evaluation of thromboembolism. For the first time, it became possible to diagnose a genetic defect (with a defined biochemical mechanism) in a substantial fraction of patients with venous thrombosis. Before the discovery of factor V Leiden, hereditary risk factors could be identified in <5% of patients presenting with VTE, even when a strong family history of thrombosis was obtained. In the current era, with widespread availability of genetic testing for factor V Leiden and another common hereditary risk factor, prothrombin 20210GA,⁴ it is now possible to identify a genetic thrombophilic factor in 10% to 20% of unselected patients with VTE and up to 50% of patients with familial thromboembolism.⁵

See p 1822

The factor V Leiden protein contains glutamine instead of arginine at amino acid 506, which is a key site of cleavage by APC. This substitution confers resistance to APC and . . . [Full Text of this Article]

Related Article:

Homozygosity for Factor V Leiden Leads to Enhanced Thrombosis and Atherosclerosis in Mice

Daniel T. Eitzman, Randal J. Westrick, Yuechun Shen, Peter F. Bodary, Shufang Gu, Sara L. Manning, Sarah L. Dobies, and David Ginsburg
Circulation 2005 111: 1822-1825. [Abstract] [Full Text]