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BMJ. 2017 Oct 26;359:j4452. doi: 10.1136/bmj.j4452.

Pregnancy, thrombophilia, and the risk of a first venous thrombosis: systematic review and bayesian meta-analysis.

Author information

1
Department of Hematology, Erasmus University Medical Centre, Postbus 2040, 3000 CA, Rotterdam, Netherlands f.croles@erasmusmc.nl.
2
Department of Hematology, Erasmus University Medical Centre, Postbus 2040, 3000 CA, Rotterdam, Netherlands.
3
Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, Rotterdam, Netherlands.
4
Department of Haematology, University Medical Centre, University of Groningen, Groningen, Netherlands.

Abstract

Objective To provide evidence to support updated guidelines for the management of pregnant women with hereditary thrombophilia in order to reduce the risk of a first venous thromboembolism (VTE) in pregnancy.Design Systematic review and bayesian meta-analysis.Data sources Embase, Medline, Web of Science, Cochrane Library, and Google Scholar from inception through 14 November 2016.Review methods Observational studies that reported on pregnancies without the use of anticoagulants and the outcome of first VTE for women with thrombophilia were eligible for inclusion. VTE was considered established if it was confirmed by objective means, or when the patient had received a full course of a full dose anticoagulant treatment without objective testing. Results 36 studies were included in the meta-analysis. All thrombophilias increased the risk for pregnancy associated VTE (probabilities ≥91%). Regarding absolute risks of pregnancy associated VTE, high risk thrombophilias were antithrombin deficiency (antepartum: 7.3%, 95% credible interval 1.8% to 15.6%; post partum: 11.1%, 3.7% to 21.0%), protein C deficiency (antepartum: 3.2%, 0.6% to 8.2%; post partum: 5.4%, 0.9% to 13.8%), protein S deficiency (antepartum: 0.9%, 0.0% to 3.7%; post partum: 4.2%; 0.7% to 9.4%), and homozygous factor V Leiden (antepartum: 2.8%, 0.0% to 8.6%; post partum: 2.8%, 0.0% to 8.8%). Absolute combined antepartum and postpartum risks for women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutations, or compound heterozygous factor V Leiden and prothrombin G20210A mutations were all below 3%. Conclusions Women with antithrombin, protein C, or protein S deficiency or with homozygous factor V Leiden should be considered for antepartum or postpartum thrombosis prophylaxis, or both. Women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutation, or compound heterozygous factor V Leiden and prothrombin G20210A mutation should generally not be prescribed thrombosis prophylaxis on the basis of thrombophilia and family history alone. These data should be considered in future guidelines on pregnancy associated VTE risk.

PMID:
29074563
PMCID:
PMC5657463
DOI:
10.1136/bmj.j4452
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisation that might have an interest in the submitted work in the previous three years. MJHAK received research funding from Ferring Pharmaceuticals, Pfizer, Daiichi Sankyo, Boehringer Ingelheim, Bayer Nederland, and Pfizer Nederland. KM received research support from Bayer, Baxter, Sanquin, and Pfizer; speaker fees from Bayer, Sanquin, Boehringer Ingelheim, and Bristol-Myers Squibb; and consulting fees from Uniqure. FWGL received consulting fees from Uniqure, Shire, and Novonordisk (fees go to the institution); unrestricted research grants from CSL Behring and Baxalta (Shire); and travel support from Roche.

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