Objective
To investigate the characteristics and outcome of abnormal vaginal bleeding in women receiving edoxaban or warfarin for treatment of venous thromboembolism (VTE).
Design and setting
Post ...hoc analysis of the Hokusai‐VTE study, a multicentre, randomised, double‐blind trial comparing edoxaban with warfarin for acute symptomatic VTE.
Population
Women below 50 years receiving edoxaban or warfarin for treatment of VTE.
Methods
We collected data on diagnostic measures, treatment, and clinical outcome of abnormal vaginal bleeding events.
Main outcome measures
Occurrence of major and clinically relevant nonmajor (CRNM) abnormal vaginal bleeding events.
Results
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.
Conclusions
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.
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Abnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin.
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Abnormal vaginal bleeding occurred more frequently in women treated with edoxaban than with warfarin.
Mixed cryoglobulinemia (MC) vasculitis represents a complication of the B cell response to a variety of chronic inflammatory diseases. Recent reports describe the use of monoclonal antibodies ...directed to CD20 antigen (rituximab), a transmembrane protein expressed on pre-B lymphocytes and mature lymphocytes. The goal of this article is therefore to review published data in order to better analyse the efficacy and tolerance of rituximab treatment in patients with MC vasculitis. After systematic review of the literature and exclusion of review papers, 13 manuscripts were identified that reported on a total number of 57 cases of MC secondary to hepatitis C virus (HCV) infection (75.4%) or essential mixed cryoglobulinemia (24.6%). Previous treatments failed to control the main signs of vasculitis; these were either HCV (n = 37) or immunomodulating treatments. Most patients (48 out of 57) received four weekly consecutive intravenous infusions of 375 mg/m(2) of rituximab. The duration of follow-up after rituximab therapy was 9.7 months. Rituximab infusions had great efficacy on the main vasculitis signs, with a clinical response in 80-93% patients. A relapse of MC was noted in 14 out of 36 (39%) patients. A relatively small number of side effects were reported. We conclude that rituximab therapy for patients with mixed cryoglobulinemia vasculitis, HCV-induced or essential, shows great efficacy on the main vasculitis signs in the majority of reported patients. A relapse of cryoglobulinemia vasculitis was frequently noted. Randomised controlled trials with long-term study are needed to form definitive conclusions on the benefit/risk ratio of rituximab therapy in such patients.
The optimal management of oral contraception and menstrual bleeding during treatment of venous thromboembolism (VTE) is largely unknown. We aimed to elicit expert opinion and compare that to current ...practice as assessed by a world-wide international web-based survey among physicians.
10 international thrombosis experts and 10 abnormal uterine bleeding experts independently completed a questionnaire containing three hypothetical patient cases each with four different scenarios, and additional queries covering different severities of VTE, patient circumstances, hormonal contraceptives and both thrombotic and bleeding complications. The consensus percentage was set a priori at ≥70%. The same questionnaire with randomized case scenarios was presented to international physicians via newsletters of the ISTH and national scientific communities. Differences between the expert groups and daily clinical care were assessed.
Expert recommendations were divergent and differed in several important points from clinical practice. In contrast to common practice in which contraceptives are discontinued at the moment of a VTE diagnosis, the thrombosis experts agreed to continue oral contraception (OC) during the anticoagulation treatment period. Also, experts reached consensus on treating patients with anticoagulation-associated abnormal uterine bleeding with tranexamic acid, although this is not supported by strong evidence from the literature. No consensus was reached on the optimal anticoagulant drug class.
International experts' opinions on handling of contraceptives and management of anticoagulant-associated abnormal uterine bleeding in female VTE patients are divergent and management in clinical practice is heterogeneous. There is a great need of further studies on these topics.
Cancer is a major risk factor for venous thromboembolism (VTE), and cancer-associated thrombosis (CAT) constitutes approximately 15-25% of all VTE cases. For decades, the standard treatment for CAT ...used to be daily subcutaneous low molecular weight heparin (LMWH). Data on the safety and efficacy of the direct oral anticoagulants (DOACs) in this population emerged only in recent years and specific DOACs were included into recent guidelines recommendations. In this narrative review of the literature, we reported the results of the phase III randomized controlled trials that evaluated the DOACs for the prevention and the acute treatment of CAT. For the acute phase treatment, the anti-Xa inhibitors (apixaban, edoxaban, rivaroxaban) showed better efficacy than LMWH in preventing VTE recurrence; however, rivaroxaban and edoxaban were also associated with an increased risk of bleeding events. For primary prevention of CAT in ambulatory cancer patients starting chemotherapy, apixaban and rivaroxaban showed better efficacy than placebo but a trend towards higher bleeding rates. Recent guidelines suggest the DOACs for the treatment of CAT in selected cancer patients (eg, low bleeding risk, no luminal gastrointestinal or genitourinary malignancies, no interfering medications). The DOACs are also suggested for primary thromboprophylaxis in selected ambulatory cancer patients at high risk of VTE (eg, Khorana score greater than or equal to2 prior to starting new chemotherapy, low bleeding risk, no interfering medications). Keywords: cancer, venous thromboembolism, apixaban, edoxaban, rivaroxaban
Essentials Clinical benefit of hospitalization vs. outpatient treatment in pulmonary embolism (PE) is unknown. We performed a propensity matched cohort study of hemodynamically stable PE patients. ...Regardless of the risk assessment, hospitalized patients had the highest rate of adverse event. If confirmed, ambulatory care of normotensive PE patients may be preferred whenever possible.
Background The decision to hospitalize or not patients with acute pulmonary embolism (PE) is controversial. Despite the advantages of close monitoring, hospitalization by itself may lead to in-hospital complications and potentially worsen the prognosis of PE patients. Objectives To determine the net clinical benefit of hospitalization vs. outpatient management of normotensive patients with acute pulmonary embolism (PE). Methods Retrospective cohort propensity score analysis (radius marching with replacement). Hemodynamically stable PE patients treated as outpatients or inpatients were matched to balance out differences for 28 patient characteristics and known risk factors for adverse events. The primary outcome was the rate of adverse events at 14 days, including recurrent venous thromboembolism, major bleeding or death. Results Among 1127 eligible patients, 1081 were included in the matched cohort, 576 treated as inpatients and 505 as outpatients. The 14-day rate of adverse events was 13.0% for inpatients and 3.3% for outpatients (adjusted OR, 5.07; 95% CI, 1.68-15.28). The 3-month rate was 21.7% for inpatients and 6.9% for outpatients (OR, 4.90; 95% CI, 2.62-9.17). In the high-risk subgroup (Pulmonary Embolism Severity Index class III-V; n = 597), the 14-day rate of adverse events was 16.5% for hospitalized patients vs. 4.5% for outpatients (OR, 4.16; 95% CI, 1.2-14.35). Conclusion Outpatient treatment of hemodynamically stable PE patients seems to be associated with a lower rate of adverse events than hospitalization and, if confirmed, may be considered as first-line management in patients not requiring specific in-hospital care, regardless of their initial risk stratification, if proper outpatient care can be provided.
Numerous studies have suggested that antipsychotic drugs are associated with an increased risk for a first episode of venous thromboembolism (VTE). However, after anticoagulation discontinuation, the ...impact of antipsychotic drugs on the risk of recurrent VTE (rVTE) remains unknown.
To estimate the risk of rVTE in association with antipsychotic drugs.
Between May 2000 and December 2012, we included all consecutive patients with a first unprovoked symptomatic VTE and who discontinued anticoagulation. During follow-up, exposure to antipsychotic drugs was systematically assessed.
A total of 736 patients with a first unprovoked symptomatic VTE were followed-up during a median period of 27.0 months (interquartile range (IQR) 6.2–60.0). Patients' median age was 66.0 years (IQR 49.0–76.0), 404 (54.9%) were men, and 61 (8.3%) were exposed to antipsychotics during follow-up. The incidence rate of r VTE was 12.1% person-year (95% CI 7.2–20.5) in antipsychotics users compared with 8.3% person-year (95% CI 7.1–9.8) in non-users (p = 0.20). Multivariate analysis showed a significant increased risk of recurrence associated with antipsychotic exposure (adjusted hazard ratio 1.9, 95% CI 1.1–3.3).
In this cohort study, exposure to antipsychotic drugs was found to be associated with an increased risk of rVTE among patients with a previous first unprovoked symptomatic VTE and who discontinued anticoagulation. Larger studies are needed to confirm and further explore this association.
•Antipsychotics may be a risk factor for first venous thromboembolism (VTE).•Impact of antipsychotics on the risk of recurrent VTE (rVTE) remains unknown.•In this cohort, we evaluated 736 patients of whom 61 were exposed to antipsychotics.•Antipsychotic users have an annual risk of rVTE of 12%.•Antipsychotic exposure was an independent risk factor for rVTE (HR 1.9, 95% CI 1.1–3.3).
Atrial fibrillation (AF) is common among patients with cancer. Patients with cancer and AF require anticoagulant therapy direct oral anticoagulants (DOAC) or vitamin K antagonist (VKA) for stroke and ...systemic embolism (SE) prevention. We sought to assess the rates of stroke/SE and major bleeding in patients with cancer and AF on oral anticoagulant therapy (DOAC or VKA).
A systematic search of MEDLINE and EMBASE was conducted. The primary efficacy and safety outcome were stroke/SE and major bleeding (as per the International Society on Thrombosis and Haemostasis definition), respectively. Incidence rates (IR) were pooled using random effects model (event per 100 patient-years). Incidence rate ratios (IRR) were computed using a Poisson regression model with associated 95% confidence intervals (CI) using R software (version 4.0.3).
Of the total 2,153 article records that were screened, 22 observational studies from 12 different countries were included in the meta-analysis (n = 94,980 patients). The IR of stroke/SE was 1.81 (95% CI: 0.89 to 3.68) and 3.41 (95% CI: 1.38 to 8.41) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.63 (95%CI: 0.47–0.84)). The IR of major bleeding was 2.59 (95%CI: 1.54 to 4.38) and 3.60 (95% CI: 1.68 to 7.71) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.76 (95% CI: 0.55 to 1.04)).
DOACs compared to VKA seem to provide a significant reduction in the risk of stroke/SE and a good risk-benefit ratio profile for safety outcomes in this patient population.
•Patients with cancer and atrial fibrillation are at high risk of stroke and bleeding.•Direct oral anticoagulants (DOACs) are associated with a lower risk of stroke compared to vitamin K antagonists.•DOACs seem to provide a good risk-benefit ratio as it may also be associated with lower risk of major bleeding.
Hereditary Protein S (PS) deficiency is a rare coagulation disorder associated with an increased risk of venous thrombosis (VT). The PS Heerlen (PSH) mutation is a rare S501P mutation that was ...initially considered to be a neutral polymorphism. However, it has been later shown that PSH has a reduced half-life in vivo which may explain the association of PSH heterozygosity with mildly reduced levels of plasma free PS (FPS). Whether the risk of VT is increased in PSH carriers remains unknown. We analyzed the association of PSH (rs121918472 A/G) with VT in 4,173 VT patients and 5,970 healthy individuals from four independent case-control studies. Quantitative determination of FPS levels was performed in a subsample of 1257 VT patients. In the investigated populations, the AG genotype was associated with an increased VT risk of 6.57 4.06-10.64 (p = 1.73 10
). In VT patients in whom PS deficiency was excluded, plasma FPS levels were significantly lower in individuals with PSH when compared to those without 72 + 13 vs 91 + 21 UI/dL; p = 1.86 10
, mean + SD for PSH carriers (n = 21) or controls (n = 1236) respectively. We provide strong evidence that the rare PSH variant is associated with VT in unselected individuals.
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