warfarin and Uterine-Hemorrhage

Antithrombotic therapies are associated with an increased bleeding risk. Abnormal uterine bleeding data have been reported in clinical trials of patients with venous thromboembolism (VTE), but data are limited for patients with atrial fibrillation (AF).. Using real-world data from four US healthcare databases (October 2010 to December 2018), we compared the occurrence of severe uterine bleeding among women newly exposed to rivaroxaban, apixaban, dabigatran, and warfarin stratified by indication.. To reduce potential confounding, patients in comparative cohorts were matched on propensity scores. Treatment effect estimates were generated using Cox proportional hazard models for each indication, in each database, and only for pairwise comparisons that met a priori study diagnostics. If estimates were homogeneous (I. Data from 363,919 women newly exposed to a direct oral anticoagulant or warfarin with a prior diagnosis of AF (60.8%) or VTE (39.2%) were analyzed. Overall incidence of severe uterine bleeding was low in the populations exposed to direct oral anticoagulants, although relatively higher in the younger VTE population vs the AF population (unadjusted incidence rates: 2.8-33.7 vs 1.9-10.0 events/1000 person-years). In the propensity score-matched AF population, a suggestive, moderately increased risk of severe uterine bleeding was observed for rivaroxaban relative to warfarin [hazard ratios and 95% confidence intervals from 0.83 (0.27-2.48) to 2.84 (1.32-6.23) across databases with significant heterogeneity], apixaban [pooled hazard ratio 1.45 (0.91-2.28)], and dabigatran [2.12 (1.01-4.43)], which were sensitive to the time-at-risk period. In the propensity score-matched VTE population, a consistent increased risk of severe uterine bleeding was observed for rivaroxaban relative to warfarin [2.03 (1.19-3.27)] and apixaban [2.25 (1.45-3.41)], which were insensitive to the time-at-risk period.. For women who need antithrombotic therapy, personalized management strategies with careful evaluation of benefits and risks are required. CLINICALTRIALS.. NCT04394234; registered in May 2020.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Observational Studies as Topic; Pyridones; Risk Assessment; Rivaroxaban; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

To investigate the characteristics and outcome of abnormal vaginal bleeding in women receiving edoxaban or warfarin for treatment of venous thromboembolism (VTE).. Post hoc analysis of the Hokusai-VTE study, a multicentre, randomised, double-blind trial comparing edoxaban with warfarin for acute symptomatic VTE.. Women below 50 years receiving edoxaban or warfarin for treatment of VTE.. We collected data on diagnostic measures, treatment, and clinical outcome of abnormal vaginal bleeding events.. Occurrence of major and clinically relevant nonmajor (CRNM) abnormal vaginal bleeding events.. In all, 628 women aged under 50 years were treated with edoxaban and 665 with warfarin. The rate of abnormal vaginal bleeding was 15/100 person-years (py) (95% CI 11-19) in women receiving edoxaban and 9/100 py (95% CI 6-12) in the warfarin group (hazard ratio: 1.7, 95% CI 1.1-2.5). Major abnormal vaginal bleeding occurred in eight (1.3%) women on edoxaban and in three (0.9%) women receiving warfarin [odds ratio (OR) 2.8; 95% CI 0.8-10.8], and CRNM abnormal vaginal bleeding occurred in 53 (8.4%) women treated with edoxaban and in 37 (5.6%) on warfarin therapy (OR 1.6, 95% CI 1.0-2.4). Over 85% of all vaginal bleeds were characterised by heavy menstrual bleeding. Major bleeds frequently required treatment, and in more than 75% of patients anticoagulant therapy was adjusted. The severity of clinical presentation and course of major and CRNM bleeds was mild in most patients.. Abnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin. Reassuringly, most events could be managed conservatively and had a mild outcome.. Abnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin.

Topics: Adult; Anticoagulants; Double-Blind Method; Female; Humans; Middle Aged; Pyridines; Thiazoles; Treatment Outcome; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

There have been reports of clinically relevant uterine bleeding events among women of reproductive age exposed to rivaroxaban.. The aim of this study was to compare the risk of severe abnormal uterine bleeding (SAUB) resulting in transfusion or surgical intervention among women on rivaroxaban versus apixaban, dabigatran and warfarin.. We conducted a retrospective cohort study in the FDA's Sentinel System (10/2010-09/2015) among females aged 18+ years with venous thromboembolism (VTE), or atrial flutter/fibrillation (AF) who newly initiated a direct oral anticoagulant (DOAC; rivaroxaban, apixaban, dabigatran) or warfarin. We followed women from dispensing date until the earliest of transfusion or surgery following vaginal bleeding, disenrollment, exposure or study end date, or recorded death. We estimated hazard ratios (HRs) using Cox proportional hazards regression via propensity score stratification. Four pairwise comparisons were conducted for each intervention.. Overall, there was an increased risk of surgical intervention with rivaroxaban when compared with dabigatran (HR 1.19; 95% CI 1.03-1.38), apixaban (1.23; 1.04-1.47), and warfarin (1.34; 1.22-1.47). No difference in risk for surgical intervention was observed for dabigatran-apixaban comparisons. Increased risk of transfusion was observed for rivaroxaban compared with dabigatran (1.49; 1.03-2.17) only. For patients with no gynecological history, rivaroxaban was associated with risk of surgical intervention compared with dabigatran (1.22; 1.05-1.42), apixaban (1.25; 1.04-1.49), and warfarin (1.36; 1.23-1.50).. Our study found increased SAUB risk with rivaroxaban use compared with other DOACs or warfarin. Increased risk with rivaroxaban was present among women without underlying gynecological conditions. Women on anticoagulant therapy should be aware of a risk of SAUB.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Uterine Hemorrhage; Warfarin

Topics: Female; Humans; Pyridines; Thiazoles; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

Essentials Factor Xa inhibitors cause more abnormal menstrual bleeding (AUB) than vitamin-K antagonists (VKA). We analyzed data of AUB in women, evaluating dabigatran versus VKA. We observed a 41% lower risk of AUB in women on dabigatran compared to those on VKA. Our findings of lower AUB risk on dabigatran should be corroborated in future studies.. Introduction Although direct oral anticoagulants (DOACs) are associated with a better safety profile than warfarin in patients with acute venous thromboembolism (VTE), direct factor Xa inhibitors involve a higher risk of abnormal uterine bleeding (AUB). We aimed to determine the risk of AUB during anticoagulation with dabigatran compared with warfarin. Methods Post-hoc analysis of the pooled RE-COVER studies and the RE-MEDY trial. Incidences of AUB, based on a defined preferred terms search for adverse events, in female patients aged 18-50 years treated with dabigatran, were compared with those in women treated with warfarin. Results Of the 2964 women included in the above-mentioned trials, 1280 women were in the relevant age category (18-50 years) and included in the current analysis. A total of 643 patients were randomized to treatment with dabigatran and 637 to treatment with warfarin. The overall rate of AUB was 8.1%, 5.9% for the women treated with dabigatran and 9.6% in those treated with warfarin, for an odds ratio for dabigatran-treated patients of 0.59 (95% confidence interval [CI], 0.39-0.90; P = 0.015). In the dabigatran-treated patients, three (0.5%) suffered major bleeding (MB) vs. five (0.8%) in the warfarin-treated patients (HR, 0.65; 95% CI, 0.15-2.72). MB or non-major relevant bleeding occurred in 30 (4.7%) patients randomized to receive dabigatran and 57 (8.9%) randomized to receive warfarin (HR, 0.53; 95% CI, 0.34-0.83). None of the bleeding events was fatal. Conclusion Dabigatran treatment was associated with a significantly (41%) lower risk of AUB than warfarin. Future studies in daily practice are needed to corroborate these findings.

Topics: Adolescent; Adult; Anticoagulants; Clinical Trials as Topic; Contraceptives, Oral, Hormonal; Dabigatran; Factor Xa Inhibitors; Female; Humans; Incidence; Menorrhagia; Middle Aged; Multicenter Studies as Topic; Uterine Hemorrhage; Venous Thromboembolism; Vitamin K; Warfarin; Young Adult

Abnormal vaginal bleeding can complicate direct oral anticoagulant (DOAC) treatment. We aimed to investigate the characteristics of abnormal vaginal bleeding in patients with venous thromboembolism (VTE) receiving apixaban or enoxaparin/warfarin. Data were derived from the AMPLIFY trial. We compared the incidence of abnormal vaginal bleeding between patients in both treatment arms and collected information on clinical presentation, diagnostic procedures, management and outcomes. In the AMPLIFY trial, 1122 women were treated with apixaban and 1106 received enoxaparin/warfarin. A clinically relevant non-major (CRNM) vaginal bleeding occurred in 28 (2.5 %) apixaban and 24 (2.1 %) enoxaparin/warfarin recipients (odds ratio [OR] 1.2, 95 % confidence interval [CI] 0.7-2.0). Of all CRNM bleeds, 28 of 62 (45 %) and 24 of 120 (20 %) were of vaginal origin in the apixaban and enoxaparin/warfarin group, respectively (OR 3.4; 95 % CI 1.8-6.7). Premenopausal vaginal bleeds on apixaban were characterised by more prolonged bleeding (OR 2.3; 95 %CI 0.5-11). In both pre- and postmenopausal vaginal bleeds, diagnostic tests were performed in six (21 %) and in seven (29 %) apixaban and enoxaparin/warfarin treated patients, respectively. Medical treatment was deemed not necessary in 16 (57 %) apixaban and 16 (67 %) enoxaparin/warfarin recipients. The severity of clinical presentation and course of the bleeds was mild in 75 % of the cases in both groups. In conclusion, although the absolute number of vaginal bleeding events is comparable between apixaban and enoxaparin/warfarin recipients, the relative occurrence of vaginal bleeds is higher in apixaban-treated women. The characteristics and severity of bleeding episodes were comparable in both treatment arms.

Topics: Administration, Oral; Adult; Anticoagulants; Blood Coagulation; Chi-Square Distribution; Factor Xa Inhibitors; Female; Humans; Logistic Models; Middle Aged; Odds Ratio; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

Topics: Adult; Anticoagulants; Drug Combinations; Factor IX; Factor VII; Factor X; Female; Humans; Leiomyoma; Prothrombin; Uterine Hemorrhage; Uterine Neoplasms; Warfarin

To determine maternal and fetal outcomes in women with mechanical heart valves managed with therapeutic dose enoxaparin during pregnancy.. Retrospective audit.. Hospital-based high-risk antenatal clinics.. Pregnant women with mechanical heart valves attending high-risk antenatal clinics, treated with enoxaparin (1 mg/kg twice daily) during pregnancy.. Women with mechanical heart valves treated with enoxaparin at any stage during pregnancy (1997-2008) identified using a database of women with mechanical heart valves attending the high-risk clinics and a prospective database of women prescribed enoxaparin for any indication during pregnancy.. Maternal outcomes included thromboembolic and haemorrhagic complications. Pregnancy and fetal outcomes included miscarriage, stillbirth, baby death and live birth, small-for-gestational-age infants, warfarin embryopathy and warfarin-related fetal loss.. Thirty-one women underwent 47 pregnancies. In 34 pregnancies (72.3%), anticoagulation was with predominantly enoxaparin and 13 (27.7%) pregnancies women received mainly warfarin, with enoxaparin given in the first trimester and/or peri-delivery. Seven (14.9%) thrombotic complications occurred, of which five (10.6%) were associated with enoxaparin treatment. Non-compliance or sub-therapeutic anti-Xa levels contributed in each case. Antenatal and postpartum haemorrhagic complications occurred in eight (17%) and 15 (32%) pregnancies respectively. Of 35 pregnancies continuing after 20 weeks' gestation, 96% (22/23) of women taking predominantly enoxaparin had a surviving infant compared with 75% (9/12) in women taking primarily warfarin. Four perinatal deaths occurred, three attributable to warfarin.. Compliance with therapeutic dose enoxaparin and aspirin during pregnancy in women with mechanical heart valves is associated with a low risk of valve thrombosis and good fetal outcomes, but close monitoring is essential.

Topics: Anticoagulants; Delivery, Obstetric; Drug Administration Schedule; Drug Monitoring; Enoxaparin; Female; Heart Valve Prosthesis; Humans; Infant, Newborn; Maternal-Fetal Exchange; Patient Compliance; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Retrospective Studies; Thromboembolism; Uterine Hemorrhage; Warfarin

Guidelines concerning the prevention and treatment of pregnancy-associated venous thromboembolism (VTE) have been elaborated by the American College of Chest Physicians and published in Chest in 2008. In this review, they have been compared with European guidelines and discussed taking into account the papers published since 2008.Most recommendations are of low grade of evidence because randomized studies are lacking during pregnancy and many reflect guidelines proposed by experts. The decisions on the most appropriate prophylaxis, dose to be administered and moment of pregnancy for starting prophylaxis are often decided case by case after careful assessment of the risk of pregnancy-associated VTE, on one hand, and the risk for the mother, on the other.Risk factors (age >or= 35, obesity, history of VTE with or without sequellae, in vitro fertilization)or thrombophilia have to be taken into account. Scores have been proposed to improve standardisation and evaluation of the risk of VTE and they should be validated.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Benzimidazoles; Blood Loss, Surgical; Cesarean Section; Contraindications; Dabigatran; Europe; Evidence-Based Medicine; Female; Fetus; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Morpholines; Polysaccharides; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Pyridines; Rivaroxaban; Societies, Medical; Thiophenes; Thrombophilia; United States; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

Topics: Anemia; Anticoagulants; Dalteparin; Delivery, Obstetric; Dextrans; Enoxaparin; Female; Hemorrhage; Humans; Length of Stay; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Sweden; Thrombophilia; Thrombosis; Uterine Hemorrhage; Warfarin

Topics: Acute Disease; Adult; Catheter Ablation; Dilatation and Curettage; Emergencies; Endometrial Hyperplasia; Female; Humans; Hysterectomy; Middle Aged; Uterine Hemorrhage; Warfarin

The advent of hysteroscopic laser surgery has provided an alternative to hysterectomy in women with menorrhagia refractory to other forms of treatment. This procedure has been used with considerable success to reproduce the signs and symptoms of Asherman's syndrome when combined with pretreatment using the synthetic steroid Danocrine (danazol). Experience with 335 patients treated with danazol, 800 mg/d, for 25 days before undergoing hysteroscopy with a neodymium:yttrium-aluminum-garnet laser demonstrated that excellent results (amenorrhea or limited spotting) were achieved in 97% of cases. All 46 patients with clotting disorders did well after surgery. The major complications associated with this procedure were fluid overload, profuse bleeding, postoperative urinary tract infections and postoperative hematometra, all of which were controlled successfully. Only one patient had to discontinue danazol treatment because of an adverse reaction.

Topics: Adolescent; Adult; Danazol; Drug Synergism; Endometriosis; Female; Humans; Hysteroscopy; Laser Therapy; Medroxyprogesterone; Medroxyprogesterone Acetate; Menorrhagia; Middle Aged; Pregnadienes; Premedication; Uterine Hemorrhage; Warfarin

Topics: Administration, Topical; Aged; Female; Humans; Male; Prothrombin Time; Salicylates; Uterine Hemorrhage; Warfarin

Topics: Adult; Anticoagulants; Female; Humans; Intrauterine Devices; Pregnancy; Thrombophlebitis; Uterine Hemorrhage; Uterine Perforation; Uterine Rupture; Warfarin

Topics: Dextrans; Female; Hematoma; Hematuria; Heparin; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombophlebitis; Uterine Hemorrhage; Vagina; Warfarin