Sunday, October 1, 2023
| 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).
| 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.
Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™
ABIM Diplomates - maximum of 1.00 ABIM MOC points
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.
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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.
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.
