Evolution of Factor V Leiden

Thijs E. van Mens; Marcel Levi; Saskia Middeldorp

doi:10.1160/TH13-02-0115

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 110(01): 23-30
DOI: 10.1160/TH13-02-0115

Review Article

Schattauer GmbH

Evolution of Factor V Leiden

Thijs E. van Mens

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

,

Marcel Levi

²Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands

,

Saskia Middeldorp

¹Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

› Author Affiliations

Abstract

Summary

Factor V Leiden is a procoagulant mutation associated with venous and arterial thrombosis and pregnancy complications. Its high prevalence of 5% in Caucasians suggests that there are evolutionary benefits as well. Carriers are indeed reported to have various advantageous phenotypes related to haemostasis, inflammation and fertility: less acute blood loss; less menstrual blood loss; decreased risk of intracranial haemorrhage; milder phenotypes of haemophilia; higher survival in and lower susceptibility to severe sepsis; higher survival in acute respiratory distress syndrome; less severe diabetic nephropathy and higher fecundity in both men and women. Not all these associations come from high quality adequately powered studies and many have not been confirmed by further research. The evolutionary influence of the alleged associations varies and is difficult to establish, partly due to a shift over time in risk factors of the diseases concerned. For most of the phenotypes possible mechanistic explanations can be provided. The procoagulant phenotype and perhaps also certain pregnancy complications follow from activated protein C (APC) resistance. Elevated APC levels possibly mediate anti-inflammatory effects. Higher sperm counts and more successful embryo implantation seem to play a role in the increased fecundity.

Keywords

Factor V Leiden - phenotype - reproduction - survival

Full Text

References

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