Family history of venous thromboembolism as a risk factor and genetic research tool

Bengt Zöller; Xinjun Li; Henrik Ohlsson; Jianguang Ji; Jan Sundquist; Kristina Sundquist

doi:10.1160/TH15-04-0306

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(05): 890-900
DOI: 10.1160/TH15-04-0306

Theme Issue Article

Schattauer GmbH

Family history of venous thromboembolism as a risk factor and genetic research tool

Authors

Bengt Zöller

¹Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
Xinjun Li

¹Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
Henrik Ohlsson

¹Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
Jianguang Ji

¹Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
Jan Sundquist

¹Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden

²Stanford Prevention Research Center, Stanford University School of Medicine, Palo Alto, California, USA
Kristina Sundquist

¹Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden

²Stanford Prevention Research Center, Stanford University School of Medicine, Palo Alto, California, USA

Abstract

Summary

Familial clustering of venous thromboembolism (VTE) was described as far back as 1905 by Briggs. Although Egeberg discovered inherited deficiency of antithrombin in 1965, it was not until Dahlback discovered resistance to activated protein C in 1993 that it became clear that genetic factors are common risk factors of VTE. Several genes have been linked to familial aggregation of VTE and genome-wide association studies have found several novel gene loci. Still, it has been estimated that much of the heritability for VTE remains to be discovered. Family history (FH) of VTE is therefore still important to determine whether a patient has an increased genetic risk of VTE. FH has the potential to represent the sum of effects and interactions between environmental and genetic factors. In this article the design, methodology, results, clinical and genetic implications of FH studies of VTE are reviewed. FH in first-degree relatives (siblings and/or parents) is associated with a 2–3 times increased familial relative risk (FRR). However, the FRR is dependent on age, number of affected relatives, and presentation of VTE (provoked/unprovoked). Especially high familial risks are observed in individuals with two or more affected siblings (FFR> 50). However, the familial risk for recurrent VTE is much lower or non-significant. Moreover, FH of VTE appears mainly to be important for venous diseases (i. e. VTE and varicose veins). The familial associations with other diseases are weaker. In conclusion, FH of VTE is an important research tool and a clinically potential useful risk factor for VTE.

Keywords

Familial thrombosis - venous thrombosis - pulmonary embolism - epidemiological studies - thrombophilia

Full Text

References

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