Risk factors for venous thromboembolism in women under combined oral contraceptive

Pierre Suchon; Fadi Al Frouh; Agathe Henneuse; Manal Ibrahim; Dominique Brunet; Marie-Christine Barthet; Marie-Françoise Aillaud; Geoffroy Venton; Marie-Christine Alessi; David-Alexandre Trégouët; Pierre-Emmanuel Morange

doi:10.1160/TH15-01-0045

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 115(01): 135-142
DOI: 10.1160/TH15-01-0045

Stroke, Systemic or Venous Thromboembolism

Schattauer GmbH Schattauer

Risk factors for venous thromboembolism in women under combined oral contraceptive

The PILl Genetic RIsk Monitoring (PILGRIM) Study

Pierre Suchon^*

¹INSERM, UMR1062, ‘Nutrition, Obesity and Risk of Thrombosis’, Aix-Marseille University, Marseille, France

²Laboratory of Hematology, APHM, Hopital Timone, Marseille, France

,

Fadi Al Frouh^*

¹INSERM, UMR1062, ‘Nutrition, Obesity and Risk of Thrombosis’, Aix-Marseille University, Marseille, France

,

Agathe Henneuse

¹INSERM, UMR1062, ‘Nutrition, Obesity and Risk of Thrombosis’, Aix-Marseille University, Marseille, France

²Laboratory of Hematology, APHM, Hopital Timone, Marseille, France

,

Manal Ibrahim

²Laboratory of Hematology, APHM, Hopital Timone, Marseille, France

,

Dominique Brunet

²Laboratory of Hematology, APHM, Hopital Timone, Marseille, France

,

Marie-Christine Barthet

²Laboratory of Hematology, APHM, Hopital Timone, Marseille, France

,

Marie-Françoise Aillaud

¹INSERM, UMR1062, ‘Nutrition, Obesity and Risk of Thrombosis’, Aix-Marseille University, Marseille, France

²Laboratory of Hematology, APHM, Hopital Timone, Marseille, France

,

Geoffroy Venton

³INSERM, UMR1090 TAGC, Aix-Marseille University, Marseille, France

⁴Service d’hématologie, APHM, Hôpital de la Conception, Marseille, France

,

Marie-Christine Alessi

¹INSERM, UMR1062, ‘Nutrition, Obesity and Risk of Thrombosis’, Aix-Marseille University, Marseille, France

²Laboratory of Hematology, APHM, Hopital Timone, Marseille, France

,

David-Alexandre Trégouët

⁵Institut National pour la Santé et la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMR_S) 1166, Paris, France

⁶Institute for Cardiometabolism and Nutrition (ICAN), Paris, France

⁷Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France

,

Pierre-Emmanuel Morange

¹INSERM, UMR1062, ‘Nutrition, Obesity and Risk of Thrombosis’, Aix-Marseille University, Marseille, France

²Laboratory of Hematology, APHM, Hopital Timone, Marseille, France

› Author Affiliations

Abstract

Summary

Identifying women at risk of venous thromboembolism (VTE) is a major public health issue. The objective of this study was to identify environmental and genetic determinants of VTE risk in a large sample of women under combined oral contraceptives (COC). A total of 968 women who had had one event of VTE during COC use were compared to 874 women under COC but with no personal history of VTE. Clinical data were collected and a systematic thrombophilia screening was performed together with ABO blood group assessment. After adjusting for age, family history, and type and duration of COC use, main environmental determinants of VTE were smoking (odds ratio [OR] =1.65, 95 % confidence interval [1.30–2.10]) and a body mass index higher than 35 kg.m^-2 (OR=3.46 [1.81–7.03]). In addition, severe inherited thrombophilia (OR=2.13 [1.32–3.51]) and non-O blood groups (OR=1.98 [1.57–2.49]) were strong genetic risk factors for VTE. Family history poorly predicted thrombophilia as its prevalence was similar in patients with or without first degree family history of VTE (29.3 % vs 23.9 %, p=0.09). In conclusion, this study confirms the influence of smoking and obesity and shows for the first time the impact of ABO blood group on the risk of VTE in women under COC. It also confirms the inaccuracy of the family history of VTE to detect inherited thrombophilia.

Keywords

Deep-vein thrombosis - oral contraceptives - thrombophilia

Full Text

References

References
1 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353: 1167-1173.
2 de Bastos M, Stegeman BH, Rosendaal FR. et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev 2014; 03: CD010813.
3 Stegeman BH, de Bastos M, Rosendaal FR. et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. Br Med J 2013; 347: f5298.
4 Lidegaard Ø, Nielsen LH, Skovlund CW. et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001–9. Br Med J 2011; 343: d6423.
5 Plu-Bureau G, Maitrot-Mantelet L, Hugon-Rodin J. et al. Hormonal contraceptives and venous thromboembolism: an epidemiological update. Best Pract Res Clin Endocrinol Metab 2013; 27: 25-34.
6 Emmerich J, Thomassin C, Zureik M. Contraceptive pills and thrombosis: effects of the French crisis on prescriptions and consequences for medicine agencies. J Thromb Haemost 2014; 12: 1388-1390.
7 Tchaikovski SN, Rosing J. Mechanisms of estrogen-induced venous thromboembolism. Thromb Res 2010; 126: 5-11.
8 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107: I4-8.
9 Murin S, Romano PS, White RH. Comparison of outcomes after hospitalisation for deep venous thrombosis or pulmonary embolism. Thromb Haemost 2002; 88: 407-414.
10 Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353: 1386-1389.
11 Cohen AT, Agnelli G, Anderson FA. et al. VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 2007; 98: 756-764.
12 Benagiano G, Bastianelli C, Farris M. Contraception today. Ann NY Acad Sci 2006; 1092: 1-32.
13 Sulak P, Lippman J, Siu C. et al. Clinical comparison of triphasic norgesti-mate/35 micrograms ethinyl estradiol and monophasic norethindrone acetate/20 micrograms ethinyl estradiol. Cycle control, lipid effects, and user satisfaction. Contraception 1999; 59: 161-166.
14 Rosenberg MJ, Meyers A, Roy V. Efficacy, cycle control, and side effects of lowand lower-dose oral contraceptives: a randomized trial of 20 micrograms and 35 micrograms estrogen preparations. Contraception 1999; 60: 321-329.
15 Royal College of Obstetricians and Gynaecologists.. Venous thromboembolism and hormonal contraception. Green-Top Guideline No. 40. July 2010.
16 HAS. Fiche Mémo. Contraception chez la femme à risque cardiovasculaire. Juillet 2013.
17 Reid R, Leyland N, Wolfman W. et al. Society of Obstetricians and Gynaecologists of Canada. SOGC clinical practice guidelines: Oral contraceptives and the risk of venous thromboembolism: an update: no. 252, December 2010. Int J Gynaecol Obstet 2011; 112: 252-256.
18 Goldhaber SZ, Grodstein F, Stampfer MJ. et al. A prospective study of risk factors for pulmonary embolism in women. J Am Med Assoc 1997; 277: 642-645.
19 Bergendal A, Bremme K, Hedenmalm K. et al. Risk factors for venous thromboembolism in pre-and postmenopausal women. Thromb Res. 2012; 130: 596-601.
20 Wu O, Robertson L, Twaddle S. et al. Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis. Br J Haematol 2005; 131: 80-90.
21 van Sluis GL, Söhne M, El Kheir DY. et al. Family history and inherited thrombophilia. J Thromb Haemost 2006; 04: 2182-2187.
22 Cosmi B, Legnani C, Bernardi F. et al. Role of family history in identifying women with thrombophilia and higher risk of venous thromboembolism during oral contraception. Arch Intern Med 2003; 163: 1105-1109.
23 Sonnevi K, Bergendal A, Adami J. et al. Self-reported family history in estimating the risk of hormone, surgery and cast related VTE in women. Thromb Res 2013; 132: 164-169.
24 Cohen W, Castelli C, Suchon P. et al. Risk assessment of venous thrombosis in families with known hereditary thrombophilia: the MARseilles-NImes prediction model. J Thromb Haemost 2014; 12: 138-146.
25 Dahlbäck B. The tale of protein S and C4b-binding protein, a story of affection. Thromb Haemost 2007; 98: 90-96.
26 Andrew M, Vegh P, Johnston M. et al. Maturation of the haemostatic system during childhood. Blood 1992; 80: 1998-2005.
27 Pernod G, Biron-Andreani C, Morange PE. et al. French group on haemostasis and thrombosis; French Society of vascular medicine. Recommendations on testing for thrombophilia in venous thromboembolic disease: a French consensus guideline. J Mal Vasc 2009; 34: 156-203.
28 Baglin T, Gray E, Greaves M. et al. British Committee for Standards in Haematology. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010; 149: 209-220.
29 Pomp ER, le Cessie S, Rosendaal FR. et al. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations. Br J Haematol 2007; 139: 289-296.
30 Bergendal A, Persson I, Odeberg J. et al. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol 2014; 124: 600-609.
31 Wu O, Bayoumi N, Vickers MA. et al. ABO(H) blood groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemost 2008; 06: 62-69.
32 van Langevelde K, Flinterman LE, van Hylckama Vlieg A. et al. Broadening the factor V Leiden paradox: pulmonary embolism and deep-vein thrombosis as 2 sides of the spectrum. Blood 2012; 120: 933-946.

Supplementary Material

Online Supplementary Material (PDF)