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Table 1.  

Patient characteristic Value
Mean age ± SD, y 34 ± 9.4
Mean BMI ± SD, kg/m 2 * 27 ± 6.8
Obese (BMI ≥30 kg/m 2 ) 25 (26%)
Index VTE diagnosis
DVT 33 (34%)
PE 45 (46%)
Both DVT and PE 20 (20%)
Unprovoked 33 (34%)
Provoked† 65 (66%)
Surgery 9
Immobilization, including hospitalization 10
Trauma 4
Travel (≥6 h), flight 6
Oral contraceptive use or hormone treatment 40
Known genetic thrombophilia 2
Hypercoagulability of other cause (COVID-19, CMV infection, nephrotic syndrome) 3
Treatment initiated at time of VTE diagnosis
Reperfusion therapy 2 (2.0%)
Anticoagulant therapy 98 (100%)
DOAC 85 (87%)
Apixaban 26 (27%)
Rivaroxaban 42 (43%)
Edoxaban 10 (10%)
Dabigatran 7 (7.1%)
Vitamin K antagonist (LMWH lead-in) 12 (12%)
LMWH 1 (1.0%)
Anticoagulant therapy at 2-mo follow-up
DOAC 85 (87%)
Apixaban 24 (25%)
Rivaroxaban 41 (42%)
Edoxaban 13 (13%)
Dabigatran 7 (7.1%)
Vitamin K antagonist 11 (11%)
LMWH 1 (1.0%)
Fondaparinux 1 (1.0%)
Anticoagulant therapy at end of follow-up
DOAC 83 (85%)
Apixaban 21 (21%)
Rivaroxaban 42 (43%)
Edoxaban 13 (13%)
Dabigatran 7 (7.1%)
Vitamin K antagonist 11 (11%)
LMWH 3 (3.1%)
Fondaparinux 1 (1.0%)
Medical history
Previous VTE 15 (15%)
Active malignancy 0
Smoking 24 (25%)
Previous gynecological findings‡ 22 (22%)
Abnormal cervical cytology or histology 2
Endometriosis 4
Ovarian cyst 3
Polycystic ovary syndrome 7
Uterine fibroid(s)/myoma(s), or polyp(s) 7
Medication use at the moment of VTE diagnosis
Anticoagulation or antiplatelet therapy 0
Oral contraceptives (estrogenic) 32 (33%)
Other hormonal contraceptives 9 (9.2%)
NuvaRing 6
Implanon 1
Evra patch 2
Intrauterine device 6 (6.1%)
Hormone-containing 5
Copper 1

Table 1. Baseline characteristics of 98 female patients of reproductive age with VTE

SD, standard deviation; BMI, body mass index; DVT, deep vein thrombosis; PE, pulmonary embolism; CMV, cytomegalovirus; DOAC, direct oral anticoagulant; LMWH, low molecular weight heparin.
*Data available in 95 patients.
†Provocative factors were not mutually exclusive. Fifteen of 98 women had more than one provocative factor: 13 women with 2 provocative factors each and 2 with 3 provocative factors each. In 12 women, VTE was provoked by the combination of oral contraceptive use/hormone treatment and another provocative factor.
‡Previous gynecological findings were not mutually exclusive. One woman had 2 gynecological findings (endometriosis and ovarian cyst).

Table 2.  

Parameter Women with AUB (n = 65)
Treatment related to AUB 21 (32%)
Medical treatment
Red blood cell transfusion 2
Intravenous iron infusion 4
Oral iron supplements 7
Reduced dose of anticoagulant 2
Temporary stop of anticoagulant 1
Tranexamic acid 1
Oral contraceptives started or intensified 8
IUD insertion* 5
Implanon insertion 1
Surgical treatment
Hysterectomy 1
Polypectomy† 1

Table 2. Details of women who received treatment related to abnormal menstrual bleeding within routine clinical care

Women could have undergone multiple medical and/or surgical treatments. AUB was defined according to at least one of the 3 definitions for AUB at at least one time during follow-up.
IUD, intrauterine device.
*Hormone (progesterone)–containing IUD in 3 women; copper IUD in 2 women.
†Planned treatment.

CME / ABIM MOC

Incidence and Impact of Anticoagulation-Associated Abnormal Menstrual Bleeding in Women After Venous Thromboembolism

  • Authors: Cindy de Jong, MD; Marc Blondon, MD, PhD; Cihan Ay, MD; Andrea Buchmüller, MD, PhD; Jan Beyer-Westendorf, MD, PhD; Judith Biechele, MD; Laurent Bertoletti, MD, PhD; Giovanna Colombo, MD, PhD; Marco Paolo Donadini, MD, PhD; Stephan V. Hendriks, MD; Luis Jara-Palomares, MD, PhD; Stephan Nopp, MD; Pedro Ruiz-Artacho, MD, PhD; Pauline Stephan, MD, PhD; Cecile Tromeur, MD, PhD; Thomas Vanassche, MD, PhD; Peter E. Westerweel, MD, PhD; Frederikus A. Klok, MD, PhD, for the TEAM-VTE investigators
  • CME / ABIM MOC Released: 10/20/2022
  • Valid for credit through: 10/20/2023
Start Activity

  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for hematologists, gynecologists, pulmonologists, internists, family practice clinicians, and other clinicians caring for women starting anticoagulant therapy because of acute venous thromboembolism, who may be at risk for abnormal uterine bleeding.

The goal of this activity is for learners to be better able to describe the incidence, prevalence, and relevance of abnormal uterine bleeding in women starting anticoagulant therapy because of acute venous thromboembolism, based on the TEAM-VTE study, an international, multicenter, prospective cohort study in women aged 18 to 50 years who were diagnosed with acute venous thromboembolism, with measurement of menstrual blood loss by Pictorial Blood Loss Assessment Charts.

Upon completion of this activity, participants will:

  • Assess incidence of any and new-onset abnormal uterine bleeding in women starting anticoagulant therapy because of acute venous thromboembolism and consequent changes in health-related quality of life, based on the TEAM-VTE study
  • Evaluate the relevant determinants and predictors of abnormal uterine bleeding in women starting anticoagulant therapy because of acute venous thromboembolism, and the effect of treatment interventions to alleviate abnormal uterine bleeding, based on the TEAM-VTE study
  • Determine the clinical implications of the incidence, prevalence, and relevance of abnormal uterine bleeding in women starting anticoagulant therapy because of acute venous thromboembolism, based on the TEAM-VTE study


Disclosures

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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.


Faculty

  • Cindy de Jong, MD

    Department of Medicine-Thrombosis and Hemostasis
    Leiden University Medical Center
    Leiden, the Netherlands

  • Marc Blondon, MD, PhD

    Division of Angiology and Hemostasis
    Geneva University Hospitals and Faculty of Medicine
    Geneva, Switzerland

  • Cihan Ay, MD

    Clinical Division of Haematology and Haemostaseology
    Department of Medicine I
    Medical University of Vienna
    Vienna, Austria

  • Andrea Buchmüller, MD, PhD

    CHU de St-Etienne
    Service de Médecine Vasculaire et Thérapeutique
    INSERM, CIC-1408
    INNOVTE
    CHU de Saint-Etienne
    Saint-Etienne, France

  • Jan Beyer-Westendorf, MD, PhD

    Division of Hematology and Hemostasis
    Department of Medicine I
    University Hospital Carl Gustav Carus
    Dresden, Germany

  • Judith Biechele, MD

    Department of Angiology
    Universitätsspital Basel
    Basel, Switzerland

  • Laurent Bertoletti, MD, PhD

    CHU de St-Etienne
    Service de Médecine Vasculaire et Thérapeutique
    INSERM, UMR1059
    Université Jean-Monnet
    INSERM, CIC-1408
    INNOVTE
    CHU de Saint-Etienne
    Saint-Etienne, France

  • Giovanna Colombo, MD, PhD

    Research Centre on Thromboembolic Disorders and Antithrombotic Therapies
    University of Insubria
    Varese, Italy

  • Marco Paolo Donadini, MD, PhD

    Department of Medicine and Surgery
    Research Centre on Thromboembolic Disorders and Antithrombotic Therapies
    University of Insubria
    Varese, Italy

  • Stephan V. Hendriks, MD

    Department of Medicine-Thrombosis and Hemostasis
    Leiden University Medical Center
    Leiden, the Netherlands

  • Luis Jara-Palomares, MD, PhD

    Medical Surgical Unit of Respiratory Diseases
    Virgen del Rocio Hospital
    Seville, Spain
    CIBER Enfermedades Respiratorias (CIBERES)
    Instituto de Salud Carlos III
    Madrid, Spain

  • Stephan Nopp, MD

    Clinical Division of Haematology and Haemostaseology
    Department of Medicine I
    Medical University of Vienna
    Vienna, Austria

  • Pedro Ruiz-Artacho, MD, PhD

    Department of Internal Medicine
    Clínica Universidad de Navarra
    Madrid, Spain
    CIBER Enfermedades Respiratorias
    Instituto de Salud Carlos III
    Madrid, Spain

  • Pauline Stephan, MD, PhD

    Department of Internal Medicine and Chest Diseases
    CHU de Brest
    GETBO UMR 1304
    Brest, France

  • Cecile Tromeur, MD, PhD

    Department of Internal Medicine and Chest Diseases
    CHU de Brest
    GETBO UMR 1304
    Brest, France

  • Thomas Vanassche, MD, PhD

    Department of Cardiovascular Sciences
    University Hospital Leuven
    Leuven, Belgium

  • Peter E. Westerweel, MD, PhD

    Department of Internal Medicine
    Albert Schweitzer Hospital
    Dordrecht, the Netherlands

  • Frederikus A. Klok, MD, PhD

    Department of Medicine-Thrombosis and Hemostasis
    Leiden University Medical Center
    Leiden, the Netherlands

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie Inc.

Editor

  • Jeanne Hendrickson, MD

    Associate Editor, Blood

Compliance Reviewer

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.


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  • Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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From Blood
CME / ABIM MOC

Incidence and Impact of Anticoagulation-Associated Abnormal Menstrual Bleeding in Women After Venous Thromboembolism

Authors: Cindy de Jong, MD; Marc Blondon, MD, PhD; Cihan Ay, MD; Andrea Buchmüller, MD, PhD; Jan Beyer-Westendorf, MD, PhD; Judith Biechele, MD; Laurent Bertoletti, MD, PhD; Giovanna Colombo, MD, PhD; Marco Paolo Donadini, MD, PhD; Stephan V. Hendriks, MD; Luis Jara-Palomares, MD, PhD; Stephan Nopp, MD; Pedro Ruiz-Artacho, MD, PhD; Pauline Stephan, MD, PhD; Cecile Tromeur, MD, PhD; Thomas Vanassche, MD, PhD; Peter E. Westerweel, MD, PhD; Frederikus A. Klok, MD, PhD, for the TEAM-VTE investigatorsFaculty and Disclosures

CME / ABIM MOC Released: 10/20/2022

Valid for credit through: 10/20/2023

processing....

Abstract and Introduction

Abstract

Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2–7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. This was an academic study registered at www.clinicaltrials.gov as #NCT04748393; no funding was received.

Introduction

Abnormal uterine bleeding (AUB) is a highly prevalent condition, affecting 10% to 30% of women of reproductive age, based on objective measurement of menstrual blood loss and self-reported information.[1] In general, abnormal menstrual bleeding is associated with negative perceptions and limited social and professional activities as well as poorer quality of life (QoL) compared with patients without abnormal menstrual bleeding: health-related QoL scores in women with AUB have been shown to be below the 25th percentile of scores for the general female population of similar age.[1–3] In addition to the burden to the individual, the conservatively estimated annual direct and indirect economic costs of AUB are approximately $1 billion and $12 billion, respectively, underlining its relevance to society at large.[1]

The prevalence of AUB in women treated with oral anticoagulants is considerably higher than in women who do not take such medications, although exact estimations of the incidence, prevalence, and impact of anticoagulation-induced AUB remain unavailable to date.[4] Data from registries and randomized trials have shown that the incidence of major uterine bleeding after initiation of anticoagulant treatment is low.[5–7] However, standard major bleeding definitions are insufficient to capture AUB because they fail to account for its chronic and recurrent nature or its major psychological impact. Several studies have suggested that the incidence of AUB is higher in patients treated with oral Xa inhibitors than in patients treated with vitamin K antagonists (VKAs) or oral thrombin inhibitors.[8–18] However, randomized trials comparing oral anticoagulant agents are unavailable, and reliable data to guide management decisions in clinical practices are lacking.

To quantify the burden of AUB and identify unmet clinical needs in women given anticoagulant therapy, we set out to acquire high-quality prospective data on the incidence, prevalence, and relevance of AUB in women starting anticoagulant therapy because of acute venous thromboembolism (VTE). More specifically, we aimed to evaluate the incidence of any AUB and new-onset AUB in these patients, consequent changes in health-related QoL, relevant determinants and predictors of AUB, and the effect of treatment interventions aimed to mitigate menstrual bleeding.