Effect of Anticoagulant Therapy for 6 Weeks vs 3 Months on Recurrence and Bleeding Events in Patients Younger Than 21 Years of Age With Provoked Venous Thromboembolism

Abstract Background The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. Methods Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. Discussion The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. Systematic review registration PROSPERO CRD42019128597.

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Real-life data of direct anticoagulant use, bleeding risk and venous thromboembolism recurrence in chronic thromboembolic pulmonary hypertension patients: an observational retrospective study

Pulmonary Circulation ◽

10.1177/2045894019873545 ◽

2020 ◽

Vol 10 (1) ◽

pp. 204589401987354 ◽

Cited By ~ 3

Author(s):

Sert Sena ◽

Mutlu Bulent ◽

Kocakaya Derya ◽

Kaptan Deniz ◽

Ataş Halil ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Real Life ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Bleeding Events ◽

Warfarin Group ◽

Thromboembolic Pulmonary Hypertension ◽

Recurrent Vte

Introduction Lifelong anticoagulation is the cornerstone of the chronic thromboembolic pulmonary hypertension (CTEPH) treatment regardless of the additional pulmonary endarterectomy, balloon pulmonary angioplasty, or medical treatment alone. Aim of this study was to evaluate the rate of oral anticoagulant preferences and document direct oral anticoagulants’ (DOACs’) safety, efficacy in the CTEPH population. Methods Patients’ demographic data obtained from database between September 2011 and April 2018. In-hospital events, death, venous thromboembolism (VTE) recurrence, bleeding events and anticoagulant therapy transition were recorded. Results We reviewed 501 CTEPH patients who observed 9.0 ± 8.5 years. All-cause death, all bleeding, recurrent VTE was observed in 15.6%, 31% and 12%. Forty-one patients (8.2%) were diagnosed as inoperable. Of all, 15.2% of operable patients remained as residual. All-cause mortality rates were 13.8% (57 pts.) in the warfarin group as compared with 9.7% (13 pts.) in rivaroxaban group (HR: 1.61, 95% CI, 0.89–2.99; p: 0.11). Higher bleeding events occurred with warfarin group (27.1%) as compared with rivaroxaban (24.6%; HR: 1.28, 95% CI, 0.86–1.88; p: 0.22). Major bleeding was significantly higher with warfarin group (HR: 1.94, 95% CI, 1.05–3.62; p: 0.03). Subgroup analysis of all-cause death revealed that this significance dominated by the rate of death according to bleeding events; warfarin versus those seen with rivaroxaban (4.85% vs. 2.2%; HR: 4.75, 95% CI: 1.12–20.16; p = 0.03). The rate of recurrent VTE was found 8.9% in the rivaroxaban group, 10.9% in warfarin group (HR: 1.21, 95% CI, 0.64–2.23; p: 0.55). Conclusion DOACs could be a safe and effective alternative for lifelong anticoagulant therapy in CTEPH patients. Rivaroxaban produced similar rates of thromboembolism and non-relevant bleeding compared to those associated with warfarin. The main difference was found with major bleeding that it was mainly associated with the death rate according to major bleeding. Using DOACs might be a more reasonable way to prevent bleeding events without increasing thromboembolic risk.

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Prediction of bleeding events using the VTE‑BLEED risk score in patients with venous thromboembolism receiving anticoagulant therapy (Review)

Experimental and Therapeutic Medicine ◽

10.3892/etm.2021.10779 ◽

2021 ◽

Vol 22 (5) ◽

Author(s):

Minerva Badescu ◽

Manuela Ciocoiu ◽

Oana Badulescu ◽

Maria-Cristina Vladeanu ◽

Iris Bojan ◽

...

Keyword(s):

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Risk Score ◽

Bleeding Events

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Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry

Thrombosis and Haemostasis ◽

10.1160/th08-03-0193 ◽

2008 ◽

Vol 100 (07) ◽

pp. 26-31 ◽

Cited By ~ 268

Author(s):

Nuria Ruíz-Giménez ◽

Carmen Suárez ◽

Rocío González ◽

José Nieto ◽

José Todolí ◽

...

Keyword(s):

Venous Thromboembolism ◽

High Risk ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Low Risk ◽

Ratio Test ◽

Validation Sample ◽

Bleeding Events ◽

Increased Risk ◽

Acute Venous Thromboembolism

SummaryA score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism (VTE). We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were randomly assigned to the derivation sample, 6,572 to the validation sample. In the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding. A score was composed assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%) patients scored 0 points (low risk); 9,645 (74%) 1–4 points (intermediate); 758 (5.8%) >4 points (high risk). The incidences of major bleeding were: 0.3% (95% confidence interval [CI]: 0.1–0.6), 2.6% (95% CI: 2.3–2.9), and 7.3% (95% CI: 5.6–9.3), respectively. The likelihood ratio test was:0.14 (95% CI:0.07–0.27) for patients at low risk;2.96 (95% CI:2.18–4.02) for those at high risk. In the validation sample the incidence of major bleeding was:0.1%,2.8%,and 6.2%,respectively. In conclusion, a risk score based on six variables documented at entry can identify VTE patients at low, intermediate, or high risk for major bleeding during the first three months of therapy.

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D-Dimer Measured at Diagnosis of Venous Thromboembolism is Associated with Risk of Major Bleeding

TH Open ◽

10.1055/s-0039-1683395 ◽

2019 ◽

Vol 03 (01) ◽

pp. e77-e84 ◽

Cited By ~ 1

Author(s):

Håkon Johnsen ◽

Kristian Hindberg ◽

Esben Bjøri ◽

Ellen Brodin ◽

Sigrid Brækkan ◽

...

Keyword(s):

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Cox Regression ◽

Bleeding Risk ◽

Predictive Biomarker ◽

Bleeding Events ◽

Vein Thrombosis ◽

Patients At Risk ◽

D Dimer

AbstractIdentification of patients at risk of major bleeding is pivotal for optimal management of anticoagulant therapy in venous thromboembolism (VTE). Studies have suggested that D-dimer may predict major bleeding during anticoagulation; however, this is scarcely investigated in VTE patients. We aimed to investigate the role of D-dimer, measured at VTE diagnosis, as a predictive biomarker of major bleeding. The study population comprised 555 patients with a first community-acquired VTE (1994–2016), who were identified among participants from the Tromsø study. Major bleeding events were recorded during the first year after VTE and defined according to the criteria of the International Society on Thrombosis and Haemostasis. Cox-regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, and duration of anticoagulant therapy. In total, 29 patients experienced major bleeding (incidence rate: 5.7/100 person-years, 95% CI: 4.0–8.2). The major bleeding risk was highest during the first 3 months, especially in patients with D-dimer ≥8.3 µg/mL (upper 20th percentile), with 28.8 major bleedings/100 person-years (95% CI: 13.7–60.4). Patients with D-dimer ≥8.3 µg/mL had a 2.6-fold (95% CI: 1.1–6.6) higher risk of major bleeding than patients with D-dimer ≤2.3 µg/mL (lower 40th percentile). Major bleeding risk according to D-dimer ≥8.3 versus ≤2.3 µg/mL was particularly pronounced among those with deep vein thrombosis (HR: 4.6, 95% CI: 1.3–16.2) and provoked events (HR: 4.2, 95% CI: 1.0–16.8). In conclusion, our results suggest that D-dimer measured at diagnosis may serve as a predictive biomarker of major bleeding after VTE, especially within the initial 3 months.

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Effectiveness of self-managed oral anticoagulant therapy in patients with recurrent venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th16-02-0088 ◽

2016 ◽

Vol 116 (09) ◽

pp. 524-529 ◽

Cited By ~ 2

Author(s):

Flemming Skjøth ◽

Erik Lerkevang Grove ◽

Peter Brønnum Nielsen ◽

Thomas Decker Christensen ◽

Torben Bjerregaard Larsen

Keyword(s):

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Oral Anticoagulant ◽

Oral Anticoagulant Therapy ◽

Vitamin K Antagonists ◽

Control Group ◽

Anticoagulant Treatment ◽

Bleeding Events ◽

Similar Frequency ◽

Recurrent Vte

SummaryPatient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross-linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42–0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44–2.02). The risk of all-cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21–0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00–1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency.Supplementary Material to this article is available online at www.thrombosis-online.com.

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Faculty Opinions recommendation of Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717969255.793469584 ◽

2013 ◽

Author(s):

David Varon

Keyword(s):

Systematic Review ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Meta Analysis

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Fondaparinux Pre-, Peri-, and/or Postpartum for the Prophylaxis/Treatment of Venous Thromboembolism (FondaPPP)

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211014575 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110145

Author(s):

Carl-Erik Dempfle ◽

Jürgen Koscielny ◽

Edelgard Lindhoff-Last ◽

Birgit Linnemann ◽

Irene Bux-Gewehr ◽

...

Keyword(s):

Venous Thromboembolism ◽

Adverse Events ◽

Drug Hypersensitivity ◽

Low Molecular Weight ◽

Premature Births ◽

First Line ◽

Bleeding Events ◽

Heparin Induced Thrombocytopenia ◽

First Line Therapy ◽

Heparin Allergy

We analyzed data for women who received fondaparinux for ≥7 days during pregnancy. The study retrospectively included women who received fondaparinux pre-, peri- and/or postpartum for ≥7 days for prophylaxis/venous thromboembolism (VTE) treatment at German specialist centers (2004-2010). Data on pregnancy, VTE risk factors, anticoagulant treatment, pregnancy outcome and adverse events were extracted from medical records. 120 women (mean age 31.5 years) were included. Among 84 women with prior pregnancies, 41.0% had ≥1 abortion. Anticoagulation was indicated for prophylaxis in 92.5% cases, including 82.5% women with an elevated VTE risk (82.8% thrombophilia, 34.2% VTE history). All women received low-molecular-weight heparin (LMWH) as first-line therapy; 3 also unfractionated heparin. Treatment changed to fondaparinux, due to heparin allergy (41.7%) or heparin-induced thrombocytopenia (10.0%). Fondaparinux was generally well tolerated. Adverse events included bleeding events (n = 5), abortion (n = 2), premature births (n = 2), stillbirth (n = 1), arrested labors (n = 2), injection site erythema (n = 4) and unspecified drug hypersensitivity (n = 6). No VTE events or increased liver enzymes occurred during treatment. In this retrospective study, fondaparinux was effective and well tolerated. Trial registration: ClinicalTrials.gov NCT01004939.

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Treatment Patterns and Clinical Outcomes in Korean Cancer Patients With Venous Thromboembolism: A Retrospective Cohort Study

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620979575 ◽

2021 ◽

Vol 27 ◽

pp. 107602962097957

Author(s):

Soo-Mee Bang ◽

Jin-Hyoung Kang ◽

Min Hee Hong ◽

Jin-Seok Ahn ◽

So Yeon Oh ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Clinical Outcomes ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Events ◽

Factors Associated ◽

Vein Thrombosis ◽

Medical Chart Review ◽

Deep Vein

This study assessed epidemiologic data and clinical outcomes, including venous thromboembolism (VTE) recurrence and bleeding events, in patients with cancer-associated VTE, and assessed factors associated with clinical outcomes. Data were extracted from retrospective medical-chart review of adult patients diagnosed with cancer-associated deep vein thrombosis or pulmonary embolism who received anticoagulation treatment for ≥3 months. Patients were classified by: low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and other anticoagulants. First VTE recurrence and bleeding events, and factors associated with their occurrence, were assessed during the initial 6 months of treatment. Overall, 623 patients (age: 63.7 ± 11.3 years, 49.3% male) were included (119, 132, and 372 patients in LMWH, DOACs and other anticoagulants groups, respectively). The cumulative 6-month incidence of VTE recurrence was 16.6% (total), 8.3% (LMWH), 16.7% (DOACs), and 20.7% (other); respective bleeding events were 22.5%, 11.0%, 12.3%, and 30.7%). VTE recurrence and bleeding rates differed only between LMWH and other anticoagulants (HR 2.4, 95% CI: 1.2-5.0 and 3.6, 1.9-6.8, respectively). These results highlight the importance of initial VTE treatment choice for preventing VTE recurrence and bleeding events. LMWH or DOACs for ≥3 months can be considered for effective VTE management in cancer patients.

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