Hamostaseologie 2020; 40(01): 012-021
DOI: 10.1055/s-0040-1701612
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Advances in Understanding Mechanisms of Thrombophilic Disorders

Björn Dahlbäck
1  Department of Translational Medicine, University Hospital, Lund University, Malmö, Sweden
› Author Affiliations
Further Information

Publication History

30 August 2019

21 October 2019

Publication Date:
28 January 2020 (online)


Venous thromboembolism constitutes a major medical problem afflicting millions of individuals worldwide each year. Its pathogenesis is multifactorial, involving both environmental and genetic risk factors. The most common genetic risk factor known to date is a mutation in the factor V (FV) gene (R506Q or FV Leiden), which impairs the normal regulation of FV by activated protein C (APC). APC is an important regulator of blood coagulation, cleaving and inactivating not only FV/FVa but also activated factor VIII (FVIIIa). In FVa, APC cleaves several sites, Arg506 (R506) being one of them. The R506Q mutation results in the APC resistance phenotype and a lifelong hypercoagulable state. A prothrombin gene mutation is another relatively frequent thrombosis risk factor, whereas deficiencies of the anticoagulant proteins antithrombin, protein C, or protein S are less common. As a result of the high prevalence of FV and prothrombin mutations in the general population, combinations of genetic defects are relatively common. Such individuals have highly increased risk of thrombosis.