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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 
1   Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France
2   Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France
3   UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France
4   Department of Obstetrics and Gynaecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
,
Chloé Bourguignon 
1   Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France
3   UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France
,
Sylvie Bouvier 
1   Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France
2   Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France
3   UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France
,
Eva Nouvellon 
1   Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France
3   UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France
,
Jeremy Laurent 
1   Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France
5   Department of Vascular Medicine, University Hospital, Montpellier, France
,
Antonia Perez-Martin 
3   UMR UA11 INSERM IDESP, Montpellier University, Montpellier, France
5   Department of Vascular Medicine, University Hospital, Montpellier, France
,
Eve Mousty 
6   Department of Gynaecology and Obstetrics, CHU Nîmes, Univ Montpellier, Nîmes, France
,
Mariya Nikolaeva 
7   Department of Obstetrics and Gynaecology, Altai State Medical University, Barnaul, Russian Federation
,
Jamilya Khizroeva 
4   Department of Obstetrics and Gynaecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
,
Victoria Bitsadze 
4   Department of Obstetrics and Gynaecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
,
Alexander Makatsariya 
4   Department of Obstetrics and Gynaecology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
› Author Affiliations Funding This work was supported by an internal grant from Nîmes University Hospital dedicated to clinical research projects on cohorts. The funder had no role in the study design, interpretation of results, or writing the report.
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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

Author Contributions

J.-C.G. conceived the study. J.-C.G., V.B., J.K., A.M., and M.N. designed the study. J.-C.G, C.B., S.B., E.N., J.L., A.P.-M., E.M., M.N., J.K., V.B, and A.M. performed the research. J.-C.G, M.N., and J.K. performed the statistical analysis. All authors contributed to data analysis and writing of the paper.


Ethical Approval

This study was approved by Nîmes University Hospital's Institutional Review Board (IRB) and ethics committee, Ivan Sechenov University's IRB in Moscow, and Altaï State Medical University's IRB in Barnaul, and performed in accordance with the policy on bioethics and human biological samples of French and Russian laws on clinical research and in accordance with the 1996 revised version of the 1975 Helsinki Declaration. All women had given their informed consent to participate.


Data Availability Statement

The dataset supporting the conclusions of this article is available in the Clinical Data Repository of Nîmes University Hospital, Place du Pr. Robert Debré, 30029 Nîmes cedex 9, France, and may be obtained by directly contacting the corresponding author.


Patient Consent

All participating authors have granted permission for publication.




Publication History

Received: 01 March 2022

Accepted: 21 April 2022

Accepted Manuscript online:
26 April 2022

Article published online:
30 June 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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