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Cited by 136Blood Coagulation and Thrombosis MechanismsVenous Thromboembolism Diagnosis and ManagementPlatelet Disorders and Treatments

Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis

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van Vlijmen, E.F.W., Wiewel‐Verschueren, S., Monster, T.B.M., Meijer, K.·2016·Journal of Thrombosis and Haemostasis
DOI 10.1111/jth.13349
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Abstract

Unlabelled Essentials We performed a meta-analysis on thrombosis risk in thrombophilic oral contraceptive (COC)-users. The results support discouraging COC-use in women with a natural anticoagulant deficiency. Contrary, additive risk of factor V Leiden (FVL) or prothrombin-G20210A (PT) mutation is modest. Women with a FVL/PT-mutation as single risk factor can use COCs if alternatives are not tolerated.Summary Background Combined oral contraceptives (COCs) are associated with an increased risk of venous thromboembolism (VTE), which is shown to be more pronounced in women with hereditary thrombophilia. Currently, WHO recommendations state that COC-use in women with hereditary thrombophilias (antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden and prothrombin-G20210A mutation) is associated with an unacceptable health risk. Objective To perform a meta-analysis evaluating the additional risk of VTE in COC-users with thrombophilia. Methods The MEDLINE and EMBASE databases were searched on 10 February 2015 for potential eligible studies. A distinction was made between 'mild' (factor V Leiden and prothrombin-G20210A mutation) and 'severe' thrombophilia (antithrombin deficiency, protein C deficiency, protein S deficiency, double heterozygosity or homozygosity of factor V Leiden and prothrombin-G20210A mutation). Results We identified 12 case-control and three cohort studies. In COC-users, mild and severe thrombophilia increased the risk of VTE almost 6-fold (rate ratio [RR], 5.89; 95% confidence interval [CI], 4.21-8.23) and 7-fold (RR, 7.15; 95% CI, 2.93-17.45), respectively. The cohort studies showed that absolute VTE risk was far higher in COC-users with severe thrombophilia than in those with mild thrombophilia (4.3 to 4.6 vs. 0.49 to 2.0 per 100 pill-years, respectively), and these differences in absolute risks were also noted in non-affected women (0.48 to 0.7 vs. 0.19 to 0.0), but with the caveat that absolute risks were estimated in relatives of thrombophilic patients with VTE (i.e. with a positive family history). Conclusion These results support discouraging COC-use in women with severe hereditary thrombophilia. By contrast, additive VTE risk of mild thrombophilia is modest. When no other risk factors are present, (e.g. family history) COCs can be offered to these women when reliable alternative contraceptives are not tolerated.

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  • In CHC users, mild thrombophilia increased the risk of VTE almost 6-fold and severe thrombophilia almost 7-fold.

    “A systematic review and meta-analysis by Van Vlijmen et al, in 2017, showed that in CHC-users, mild or severe thrombophilia increased the risk of VTE almost 6-fold and 7-fold respectively.”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [111]

  • The absolute VTE risk was far higher in CHC users with severe thrombophilia (4.3-4.6/100 pill-years) than in those with mild thrombophilia (0.5-2.0/100 pill-years).

    “The absolute VTE risk was far higher in CHC-users with severe thrombophilia (4.3 – 4.6/100 pill-years) than in those with mild thrombophilia (0.5 – 2.0/100 pill-years). [111]”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [111]

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Authors
van Vlijmen, E. F. W., Wiewel‐Verschueren, S., Monster, T. B. M., & Meijer, K.
Affiliations
University Medical Center Groningen (NL)
ORCID
Venue
Journal of Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2016-07
Volume
14
Issue
7
Pages
1393-1403
ISSN
1538-7836 (ISSN-L)
DOI
10.1111/jth.13349
OpenAlex
W2343741170
Cited by
136
References
45
Citations by year
2026: 14 · 2025: 14 · 2024: 18 · 2023: 19 · 2022: 13 · 2021: 8 · 2020: 14 · 2019: 15 · 2018: 11 · 2017: 7 · 2016: 2
FWCI
1.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thrombosis and Haemostasis (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
Keywords
combined oral contraceptives, venous thromboembolism, thrombophilia, factor V Leiden, prothrombin G20210A, antithrombin deficiency, protein C deficiency, protein S deficiency, inherited thrombophilia, VTE risk, anticoagulant deficiency, double heterozygosity, homozygosity, oral contraceptive use
MeSH terms
Adolescent, Adult, Aged, Anticoagulants, Contraceptives, Oral, Combined, Factor V, Female, Heterozygote, Humans, Middle Aged, Mutation, Prothrombin, Risk Factors, Cohort Studies, Case-Control Studies, Protein S Deficiency, Thrombophilia, Protein C Deficiency, Venous Thromboembolism, Young Adult

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