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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

Bengt Zöller
1   Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
,
Xinjun Li
1   Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
,
Henrik Ohlsson
1   Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
,
Jianguang Ji
1   Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
,
Jan Sundquist
1   Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
2   Stanford Prevention Research Center, Stanford University School of Medicine, Palo Alto, California, USA
,
Kristina Sundquist
1   Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden
2   Stanford Prevention Research Center, Stanford University School of Medicine, Palo Alto, California, USA
› Author Affiliations
Further Information

Publication History

Received: 13 April 2015

Accepted after minor revision: 03 July 2015

Publication Date:
06 December 2017 (online)

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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
 

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