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
1  Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Marcel Levi
2  Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands
Saskia Middeldorp
1  Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 11 February 2013

Accepted after major revision: 13 April 2013

Publication Date:
30 November 2017 (online)


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.