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CC BY 4.0 · TH Open 2019; 03(01): e28-e35
DOI: 10.1055/s-0039-1677807
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Common Risk Factors Add to Inherited Thrombophilia to Predict Venous Thromboembolism Risk in Families

Pierre Suchon
1   Laboratory of Haematology, La Timone Hospital, Marseille, France
2   C2VN, Aix Marseille University, Marseille, France
,
Noemie Resseguier
3   Support Unit for Clinical Research and Economic Evaluation, Assistance Publique - Hôpitaux de Marseille, Marseille, France
4   EA3279 Self-perceived Health Assessment Research Unit, Aix-Marseille University, Marseille, France
,
Manal Ibrahim
1   Laboratory of Haematology, La Timone Hospital, Marseille, France
2   C2VN, Aix Marseille University, Marseille, France
,
Alexia Robin
1   Laboratory of Haematology, La Timone Hospital, Marseille, France
,
Geoffroy Venton
5   Aix-Marseille Université, TAGC Campus de Luminy, Marseille, France
6   Department of Hematology and Cellular Therapy, AP-HM, Conception Hospital, Marseille, France
,
Marie-Christine Barthet
1   Laboratory of Haematology, La Timone Hospital, Marseille, France
,
Dominique Brunet
1   Laboratory of Haematology, La Timone Hospital, Marseille, France
,
Noemie Saut
1   Laboratory of Haematology, La Timone Hospital, Marseille, France
,
Marie-Christine Alessi
1   Laboratory of Haematology, La Timone Hospital, Marseille, France
2   C2VN, Aix Marseille University, Marseille, France
,
David A. Trégouët   *
7   Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France
,
Pierre E. Morange   *
1   Laboratory of Haematology, La Timone Hospital, Marseille, France
2   C2VN, Aix Marseille University, Marseille, France
› Author Affiliations
Further Information

Publication History

20 September 2018

21 December 2018

Publication Date:
28 January 2019 (online)

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Abstract

The clinical venous thromboembolism (VTE) pattern often shows wide heterogeneity within relatives of a VTE-affected family, although they carry the same thrombophilia defect. It is then mandatory to develop additional tools for assessing VTE risk in families with thrombophilia. This study aims to assess whether common environmental and genetic risk factors for VTE contribute to explain this heterogeneity. A total of 2,214 relatives from 651 families with known inherited thrombophilia were recruited at the referral center for thrombophilia in Marseilles, France, from 1986 to 2013. A thrombophilia screening was systematically performed in all included relatives. According to the severity of the thrombophilia defect, individuals were split into three groups: no familial defect, mild thrombophilia, and severe thrombophilia. In addition, common genetic factors (ABO blood group and 11 polymorphisms selected on the basis of their association with VTE in the general population) were genotyped. Furthermore, body mass index and smoking were collected. VTE incidence was 1.74, 3.64, and 6.40 per 1,000 person-years in individuals with no familial defect, mild thrombophilia, and severe thrombophilia, respectively. Five common risk factors were associated with VTE in this population: obesity, smoking, ABO blood group, and F11_rs2036914 and FGG_rs2066865 polymorphisms. These common factors were then included into a three-level risk score. The score was highly efficient for assessing VTE risk in mild thrombophilia patients by identifying two groups with different VTE risk; individuals with low score had the same risk as individuals with no familial defect whereas individuals with high score had the same risk as individuals with severe thrombophilia. An overall score including the five items plus the thrombophilia status was built and displayed an area under the receiver operating characteristic curve of 0.702 for discriminating VTE and non-VTE relatives. In conclusion, integrating common environmental and genetic risk factors improved VTE risk assessment in relatives from families with thrombophilia.

Keywords

family medical history - single nucleotide polymorphism - risk assessment - thrombophilia - venous thromboembolism

Supplementary Material

 

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