CoChat
Sign Up
Cited by 219Venous Thromboembolism Diagnosis and ManagementBlood Coagulation and Thrombosis MechanismsAtrial Fibrillation Management and Outcomes

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use

Open access
Martinelli, Ida, Lensing, Anthonie W. A., Middeldorp, Saskia, Levi, Marcel, Beyer-Westendorf, Jan, van Bellen, Bonno, Bounameaux, Henri, Brighton, Timothy A. +6 more·2016·Blood
DOI 10.1182/blood-2015-08-665927PMC PMC4832477
Open this paper in CoChat — free accountOpen PDF

Abstract

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1182/blood-2015-08-665927

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In a study by Martinelli et al, women who were on anticoagulation and used CHCs were no more likely to suffer recurrent VTE than women who used progestin-only contraceptives or no hormonal contraceptives.

    “In a study by Martinelli et al, which analyzed data from the EINSTEIN DVT and Pulmonary Embolism (PE) anticoagulation trials found that women who were on anticoagulation and used CHCs were no more likely to suffer recurrent VTE than women who used progestin-only contraceptives or no hormonal contraceptives[106].”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [106]

  • CHCs did not increase the risk of thrombosis in women who were on therapeutic anticoagulation.

    “The study concluded that CHCs did not increase the risk of thrombosis in women who were on therapeutic anticoagulation.”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [106]

  • With therapeutic anticoagulation, estrogen therapy can be safely continued in cisgender women who develop VTE on estrogen.

    “Prospective data suggests that with therapeutic anticoagulation, estrogen therapy can be safely continued in cisgender women who develop VTE on estrogen [106].”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [106]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 50 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Martinelli, I., Lensing, A. W. A., Middeldorp, S., Levi, M., Beyer-Westendorf, J., van Bellen, B., Bounameaux, H., Brighton, T. A., Cohen, A. T., Trajanovic, M., Gebel, M., Lam, P., Wells, P. S., & Prins, M. H.
Affiliations
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
  • Bayer (Germany) (DE)
  • Amsterdam UMC Location University of Amsterdam (NL)
  • University Hospital “Carl Gustav Carus,” Technische Universität Dresden, Dresden, Germany;
  • Department of Vascular Surgery, Beneficencia Portuguesa Hospital, São Paulo, Brazil;
  • University Hospital of Geneva (CH)
  • Prince of Wales Hospital (AU)
  • National Health Service (GB)
  • Bayer (United States) (US)
  • Bayer HealthCare, Ho Chi Minh, Vietnam;
  • University of Ottawa (CA)
  • Maastricht University Medical Centre (NL)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2016-03-17
Volume
127
Issue
11
Pages
1417-1425
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2015-08-665927
PMC
PMC4832477
OpenAlex
W2205757214
Cited by
219
References
50
Citations by year
2026: 17 · 2025: 21 · 2024: 23 · 2023: 13 · 2022: 14 · 2021: 21 · 2020: 26 · 2019: 20 · 2018: 29 · 2017: 18 · 2016: 17
FWCI
21.73
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion)
  • Pure Amsterdam UMC (acceptedVersion, other-oa)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Bristol-Myers Squibb
  • Pfizer
  • GlaxoSmithKline
  • Sanofi
  • Government of the United Kingdom
  • Bayer HealthCare
  • Daiichi Sankyo Europe
Topics
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
Keywords
recurrent venous thromboembolism, abnormal uterine bleeding, hormonal contraception, estrogen-containing contraceptives, progestin-only contraception, vitamin K antagonists, rivaroxaban, enoxaparin, anticoagulation, post-thrombotic syndrome
MeSH terms
Rivaroxaban, Adult, Anticoagulants, Contraceptives, Oral, Hormonal, Drug Synergism, Estrogens, Female, Humans, Middle Aged, Progestins, Recurrence, Retrospective Studies, Uterine Hemorrhage, Estrogen Replacement Therapy, Proportional Hazards Models, Randomized Controlled Trials as Topic, Enoxaparin, Venous Thromboembolism, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review