Pregnancy after Combined Oral Contraceptive-Associated Venous Thromboembolism: An International Retrospective Study of Outcomes

Jean-Christophe Gris; Chloé Bourguignon; Sylvie Bouvier; Eva Nouvellon; Jeremy Laurent; Antonia Perez-Martin; Eve Mousty; Mariya Nikolaeva; Jamilya Khizroeva; Victoria Bitsadze; Alexander Makatsariya

doi:10.1055/a-1835-8808

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2022; 122(10): 1779-1793
DOI: 10.1055/a-1835-8808

Stroke, Systemic or Venous Thromboembolism

Pregnancy after Combined Oral Contraceptive-Associated Venous Thromboembolism: An International Retrospective Study of Outcomes

Jean-Christophe Gris

¹Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France

²Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France

³UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France

⁴Department of Obstetrics and Gynaecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

,

Chloé Bourguignon

¹Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France

³UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France

,

Sylvie Bouvier

¹Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France

²Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France

³UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France

,

Eva Nouvellon

¹Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France

³UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France

,

Jeremy Laurent

¹Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France

⁵Department of Vascular Medicine, University Hospital, Montpellier, France

,

Antonia Perez-Martin

³UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France

⁵Department of Vascular Medicine, University Hospital, Montpellier, France

,

Eve Mousty

⁶Department of Gynaecology and Obstetrics, CHU Nîmes, Univ Montpellier, Nîmes, France

,

Mariya Nikolaeva

⁷Department of Obstetrics and Gynaecology, Altai State Medical University, Barnaul, Russian Federation

,

Jamilya Khizroeva

⁴Department of Obstetrics and Gynaecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

,

Victoria Bitsadze

⁴Department of Obstetrics and Gynaecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

,

Alexander Makatsariya

⁴Department of Obstetrics and Gynaecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

› Author Affiliations

Abstract

Background Few data are available on thrombotic outcomes during pregnancy and puerperium occurring after an initial provoked venous thromboembolic (VTE) event.

Objectives To describe thrombotic outcomes during pregnancy after a first combined oral contraceptive (COC)-associated VTE and the factors associated with recurrence.

Methods This was an international multicentric retrospective study on patients referred for thrombophilia screening from January 1, 2010 to January 1, 2021 following a first COC-associated VTE, including women with neither inherited thrombophilia nor antiphospholipid antibodies and focusing on those who had a subsequent pregnancy under the same thromboprophylaxis treatment. Thrombotic recurrences during pregnancy and puerperium as well as risk factors for recurrence were analyzed.

Results We included 2,145 pregnant women. A total of 88 thrombotic events, 58 antenatal and 29 postnatal, occurred, mostly during the first trimester of pregnancy and the first 2 weeks of puerperium. Incidence rates were 49.6 (37–62) per 1,000 patient-years during pregnancy and 118.7 (78–159) per 1,000 patient-years during puerperium. Focusing on pulmonary embolism, incidence rates were 1.68 (1–4) per 1,000 patient-years during pregnancy and 65.5 (35–97) per 1,000 patient-years during puerperium.

Risk factors for antenatal recurrences were maternal hypercholesterolemia and birth of a very small-for-gestational-age neonate. A risk factor for postnatal recurrence was the incidence of preeclampsia.

Conclusion Our multicentric retrospective data show significant rates of VTE recurrence during pregnancy and puerperium in women with a previous VTE event associated with COC, despite a unique low-molecular-weight heparin-based thromboprophylaxis. These results may provide benchmarks and valuable information for designing future randomized controlled trials.

Keywords

combined oral contraceptives - venous thrombosis - pregnancy - recurrence - prognosis

Full Text

References

References
1 Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12 (08) 464-474
2 Blanco-Molina A, Trujillo-Santos J, Tirado R. et al; RIETE Investigators. Venous thromboembolism in women using hormonal contraceptives. Findings from the RIETE Registry. Thromb Haemost 2009; 101 (03) 478-482
3 Hugon-Rodin J, Horellou MH, Conard J, Flaujac C, Gompel A, Plu-Bureau G. and for the COntraception, REcurrent Venous Event (COREVE) investigators. First venous thromboembolism and hormonal contraceptives in young French women. Medicine (Baltimore) 2017; 96 (34) e7734
4 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. BMJ 2013; 347: f5298
5 Teal S, Edelman A. Contraception selection, effectiveness, and adverse effects: a review. JAMA 2021; 326 (24) 2507-2518
6 Eischer L, Eichinger S, Kyrle PA. The risk of recurrence in women with venous thromboembolism while using estrogens: a prospective cohort study. J Thromb Haemost 2014; 12 (05) 635-640
7 Galanaud JP, Sevestre MA, Pernod G. et al; OPTIMEV-SFMV Investigators. Epidemiology and 3-year outcomes of combined oral contraceptive-associated distal deep vein thrombosis. Res Pract Thromb Haemost 2020; 4 (07) 1216-1223
8 Wiegers HMG, Knijp J, van Es N. et al. Risk of recurrence in women with venous thromboembolism related to estrogen-containing contraceptives: systematic review and meta-analysis. J Thromb Haemost 2022; 20 (05) 1158-1165
9 Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton III LJ. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143 (10) 697-706
10 Bukhari S, Fatima S, Barakat AF, Fogerty AE, Weinberg I, Elgendy IY. Venous thromboembolism during pregnancy and postpartum period. Eur J Intern Med 2022; 97: 8-17
11 Nichols KM, Henkin S, Creager MA. Venous thromboembolism associated with pregnancy: JACC Focus Seminar. J Am Coll Cardiol 2020; 76 (18) 2128-2141
12 De Stefano V, Martinelli I, Rossi E. et al. The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis. Br J Haematol 2006; 135 (03) 386-391
13 Pabinger I, Grafenhofer H, Kaider A. et al. Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis. J Thromb Haemost 2005; 3 (05) 949-954
14 Galambosi PJ, Ulander VM, Kaaja RJ. The incidence and risk factors of recurrent venous thromboembolism during pregnancy. Thromb Res 2014; 134 (02) 240-245
15 Lazo-Langner A, Al-Ani F, Weisz S. et al. Prevention of venous thromboembolism in pregnant patients with a history of venous thromboembolic disease: a retrospective cohort study. Thromb Res 2018; 167: 20-25
16 Roeters van Lennep JE, Meijer E, Klumper FJ, Middeldorp JM, Bloemenkamp KW, Middeldorp S. Prophylaxis with low-dose low-molecular-weight heparin during pregnancy and postpartum: is it effective?. J Thromb Haemost 2011; 9 (03) 473-480
17 Christiansen SC, Lijfering WM, Helmerhorst FM, Rosendaal FR, Cannegieter SC. Sex difference in risk of recurrent venous thrombosis and the risk profile for a second event. J Thromb Haemost 2010; 8 (10) 2159-2168
18 de Moreuil C, Tromeur C, Daoudal A. et al. Risk factors for recurrence during a pregnancy following a first venous thromboembolism: A French observational study. J Thromb Haemost 2022; 20 (04) 909-918
19 Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis. Chest 2012; 141 (2, Suppl): e691S-e736S
20 Royal College of Obstetricains and Gynaecologists. Green Top Guideline No. 37a. Reducing the risk of venous thromboembolism during pregnancy and the puerperium. 2015 Accessed February 2022 at: https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/reducing-the-risk-of-thrombosis-and-embolism-during-pregnancy-and-the-puerperium-green-top-guideline-no-37a/
21 Bain E, Wilson A, Tooher R, Gates S, Davis LJ, Middleton P. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane Database Syst Rev 2014; (02) CD001689
22 Pengo V, Tripodi A, Reber G. et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009; 7 (10) 1737-1740
23 Devreese KMJ, Ortel TL, Pengo V, de Laat B. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost 2018; 16 (04) 809-813
24 Ageno W, Squizzato A, Wells PS, Büller HR, Johnson G. The diagnosis of symptomatic recurrent pulmonary embolism and deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost 2013; 11 (08) 1597-1602
25 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
26 World Health Organization. WHO recommendations for the prevention and treatment of postpartum haemorrhage. Geneva: World Health Organization; Department of Making Pregnancy Safer; 2014 Accessed February 2022 at: http://apps.who.int/iris/bitstream/10665/75411/1/9789241548502_eng.pdf
27 Rodger MA, Kahn SR, Wells PS. et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008; 179 (05) 417-426
28 Gris JC, Bouvier S, Molinari N. et al. Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood 2012; 119 (11) 2624-2632
29 Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G. et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood 2014; 123 (03) 404-413
30 Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6 (06) 905-912
31 Sultan AA, Tata LJ, West J. et al. Risk factors for first venous thromboembolism around pregnancy: a population-based cohort study from the United Kingdom. Blood 2013; 121 (19) 3953-3961
32 Kourlaba G, Relakis J, Kontodimas S, Holm MV, Maniadakis N. A systematic review and meta-analysis of the epidemiology and burden of venous thromboembolism among pregnant women. Int J Gynaecol Obstet 2016; 132 (01) 4-10
33 Virkus RA, Løkkegaard EC, Bergholt T, Mogensen U, Langhoff-Roos J, Lidegaard Ø. Venous thromboembolism in pregnant and puerperal women in Denmark 1995-2005. A national cohort study. Thromb Haemost 2011; 106 (02) 304-309
34 Sultan AA, West J, Tata LJ, Fleming KM, Nelson-Piercy C, Grainge MJ. Risk of first venous thromboembolism in and around pregnancy: a population-based cohort study. Br J Haematol 2012; 156 (03) 366-373
35 Spasić I, Ubavić M, Šumarac Z, Todorović M, Vučković B. Influence of lipid metabolism disorders on venous thrombosis risk. J Med Biochem 2021; 40 (03) 245-251
36 Blondon M, Quon BS, Harrington LB, Bounameaux H, Smith NL. Association between newborn birth weight and the risk of postpartum maternal venous thromboembolism: a population-based case-control study. Circulation 2015; 131 (17) 1471-1476 , discussion 1476
37 Opichka MA, Rappelt MW, Gutterman DD, Grobe JL, McIntosh JJ. Vascular Dysfunction in Preeclampsia. Cells 2021; 10 (11) 3055