Rate Of Recurrent Venous Thromboembolism Research Articles

Outpatient Management of Cancer-Associated Pulmonary Embolism: A Systematic Review and Meta-Analysis.

Outpatient management of pulmonary embolism (PE) remains controversial in patients with cancer due to their higher risks of mortality, recurrent venous thromboembolism (VTE) and bleeding complications. This systematic review and meta-analysis aimed to evaluate the safety and feasibility of outpatient management of cancer-associated PE. We searched MEDLINE, Embase, Cochrane Central, and Scopus databases from inception to May 30, 2024, for studies on outpatient management of cancer-associated PE. Eligible studies included randomized controlled trials, cohort studies, and case-control studies with ≥10 patients. The primary outcome was 30-day-all-cause mortality; secondary outcomes included VTE-related mortality, major bleeding and recurrent VTE at 30 days. Meta-analysis was performed using random effects models, and heterogeneity was assessed with the I2 statistic. Nineteen studies (13 full-article, 6 abstract-only) with a total of 1589 patients managed as outpatients were identified. Criteria for outpatient management of cancer-associated PE were reported in 14 studies. The pooled 30-day all-cause mortality rate was 1.74% (95% CI: 0.99-3.03; I2=0%, 691 patients, 6 full-article). The 30-day major bleeding pooled rate was 2.71% (95% CI: 1.51-4.83; I2=0%; 406 patients, 6 full-article), and the 30-day recurrent VTE pooled rate was 1.26% (95% CI: 0.53-3.00; I2=0%; 396 patients, 5 full-article). Selected patients with cancer-associated PE managed as outpatients appear to have low short-term rates of mortality, major bleeding and recurrent VTE suggesting this may be a safe strategy. Further research with larger, prospective studies is needed to confirm these findings and refine risk stratification protocols.

Comparative analysis of the efficacy of direct oral anticoagulant rivaroxaban and low molecular weight heparin in the treatment of tumor patients with venous thromboembolism

Objective: To explore the effectiveness and safety of direct oral anticoagulant rivaroxaban and low molecular weight heparin (LMWH) in the treatment of tumor patients with venous thromboembolism (VTE). Methods: A retrospective analysis was conducted on 296 patients diagnosed with tumor associated VTE in the Shanghai Pulmonary Thromboembolism Database from December 2020 to September 2022. Patients were grouped according to the prescription of anticoagulant drugs. Thirteen baseline variables [age, gender, smoking history, physical state (PS) score, tumor type, tumor stage, tumor treatment method, hemoglobin, platelets, D-dimer, creatinine, alanine aminotransferase, and VTE site] were matched. After matching, 100 cases were assigned to rivaroxaban group, including 64 males and 36 females, aged [M (Q1, Q3)] 70 (62,74) years old; There were 100 cases in the LMWH group, including 69 males and 31 females, aged 68 (60,73) years old. Kaplan-Meier method was used to plot survival curves. The differences between the rivaroxaban group and LMWH group in 6-month cumulative VTE recurrence rate, clinically significant bleeding rate, and all-cause mortality rate were analysed using log-rank test. Results: There were no statistically significant differences between the rivaroxaban group and the LMWH group in the 6-month cumulative VTE recurrence rate [13.5% (95%CI: 6.4%-20.1%) vs 7.5% (95%CI: 2.0%-12.7%), P=0.171], bleeding incidence rate [9.2% (95%CI: 3.3%-14.8%) vs 6.2% (95%CI: 1.3%-10.9%), P=0.438] and all-cause mortality rate [8.0% (95%CI: 2.5%-13.2%) vs 10.0% (95%CI: 3.9%-15.7%), P=0.602]. Conclusion: The anticoagulant efficacy and safety of rivaroxaban and LMWH are comparable in tumor patients with VTE.

Reduced- versus full-dose anticoagulants for the extended treatment of cancer-associated venous thromboembolism in Thai patients

BackgroundReduced dose anticoagulant therapy for the extended treatment of cancer-associated venous thromboembolism (VTE) has been used to avoid bleeding. However, it may increase the risk of recurrent VTE. AimsTo study the rate of recurrent VTE and bleeding complications in Thai patients with cancer-associated VTE who were treated with full-dose or reduced-dose anticoagulants. MethodsA retrospective cohort study was conducted in a single-center academic hospital. Electronic medical records were reviewed from 2016-2023. Patients with cancer-associated VTE who received anticoagulants for at least 3 months were evaluated. Reduced-dose anticoagulant was defined as a dose that was lower than the recommended standard dosage. The primary outcome was recurrent VTE. The secondary outcomes were major bleeding and clinically relevant non-major bleeding. ResultsA total of 229 patients were included. The median age was 65 years (interquartile range [IQR] 54-72). In the reduced-dose group, age and history of previous bleeding were higher than in the full-dose group. There were 169 (74%) patients and 60 (26%) patients who received full- and reduced-dose anticoagulants. The median time to reduce the dose was 3.6 months ([IQR] 0.7 – 5.5). Of a total of 7 (3.1%) recurrent VTE, 4 (2.4%) occurred in the full-dose and 3 (5.0%) in the reduced-dose groups (p=0.4), respectively. The median time to recurrent VTE was 7.2 months ([IQR] 3.5-12.4). There were 8 (3.5%) bleeding events, 7 (4.1%) and 1 (1.7%) in the full and reduced-dose anticoagulant groups (p=0.35), respectively. The median follow-up time was 1.5 years (IQR 1-3.1). ConclusionOlder age and a history of previous bleeding were associated with the use of reduced-dose anticoagulants. Patients with cancer-associated VTE receiving reduced-dose anticoagulants had a numerically higher risk of recurrent VTE and lower bleeding outcomes compared with those receiving full-dose anticoagulants.

Routine use of ultrasound-assisted catheter-directed thrombolysis for the management of intermediate-high risk pulmonary embolism: a service evaluation project

Abstract Background Intermediate-high risk Pulmonary Embolism (PE) has considerable morbidity. Conservative management could be sub-optimal. Ultrasound-Assisted Catheter-Directed Thrombolysis (UACDT) is used in our centre for the routine management of this presentation. Purpose We assessed the procedure safety and short-term outcomes by reviewing locally performed procedures. Methods This is an observational retrospective cohort study, with a historic control group. Our centre is a District General Hospital (DGH) in the United Kingdom, and we receive referrals from local acute hospitals. Since the introduction of this service in June 2018 until November 2023, 129 patients (2 patients/month) received routine management with UACDT for intermediate-high risk PE. The controls are 75 acute PE patients of comparable risk classes, managed from January to December 2016. We assessed procedural and in-hospital outcomes including minor, major bleeding/complications and death. We also assessed Length of Stay (LoS) in hospital, recurrent Venous Thrombo-Embolism (VTE) and re-admission rates for recurrent PE at 30 days. Reduction of oxygen requirements and improved estimated systolic Pulmonary Artery Pressure (sPAP) post-procedure were assessed as surrogate measures. Continuous variables were analysed with a Mann-Whitney U test, and categorical variables with a Chi-square Test. Results Baseline demographics are listed in Table 1. Mean duration between CT Pulmonary Angiography (CTPA) and the UACDT procedure was 1.6 (±SD 1.4) days, including inter-hospital transfer. Only 6% (8/129) of UACDT cohort received ≤12 mg standard alteplase dose. In the control group, 4% (3/75) of patients received standard 100mg systemic thrombolysis. There was no significant difference in the rates of minor (p= 0.9), major bleeding/complications (p= 0.8), or death (p= 1.0) between both groups. There was also no significant difference in rates of recurrent VTE (p= 1.0) or re-admission within 30 days for PE (p=0.1) (Table 2). LoS in hospital data were ratified, to exclude inappropriate delays (e.g. physiotherapy requirements, etc). We used the date when the patient was declared medically fit for discharge, and no significant difference was noted (p= 0.2). This was confirmed with a regression analysis of UACDT treatment effect (p= 0.9, CI= -3.5 to 3.1). Nonetheless, there was a 25% reduction of median LoS in hospital from 8 days in the controls to 6 days with UACDT. The proportion of patients requiring O2 was also reduced from 69% (89/129) to 41% (54/129) on day 1 post-procedure. A significant reduction of the estimated sPAP by TTE post-procedure was detected by a mean of 10.4 (±SD 13.9) mmHg (p= <0.01). Conclusion UACDT is generally safe with low complications rate. Compared to the control group, there was a reduction in absolute deaths and median LoS in hospital. This can be secondary to the significant acute reduction of systolic pulmonary artery pressure identified.

Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban in major-thrombophilia carriers.

Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5mg BID or rivaroxaban 10mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14-p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk.

AN UPDATE ON DIAGNOSIS AND MANAGEMENT OF THROMBOEMBOLISM IN PREGNANCY

Thromboembolism during pregnancy poses a significant challenge in maternal healthcare, substantially contributing to maternal morbidity and mortality worldwide. Understanding its diagnosis and management is crucial for improving maternal and fetal outcomes. Objective: To evaluate the diagnosis and management of thromboembolism in pregnant women. Methods: A retrospective cohort study was conducted at Lady Reading Hospital, Peshawar, from July 2022 to July 2024. The study included 175 pregnant females diagnosed with venous thromboembolism (VTE) during their pregnancy. Data were collected on patient demographics, trimester of diagnosis, type of thromboembolism (deep vein thrombosis [DVT] or pulmonary embolism [PE]), treatment modalities, and outcomes. Patients were treated with either low molecular weight heparin (LMWH) or unfractionated heparin (UFH). Descriptive statistics were used to analyze the data, with results presented as percentages and means with standard deviations. Results: The mean age of the participants was 32.01 ± 2.35 years. Thromboembolism was most commonly diagnosed in the third trimester (65%), followed by the second trimester (25%) and the first trimester (10%). DVT was observed in 74% of patients, while PE occurred in 26%. Among the 160 patients treated with LMWH, 3% (5 patients) experienced a recurrence of VTE. Of the 15 patients who received UFH, 5% (8 patients) had significant bleeding complications. Overall maternal outcomes included a 3% recurrence rate of VTE and a 5% rate of significant bleeding complications. No maternal mortality was reported. Conclusion: Early diagnosis and timely management of thromboembolism in pregnancy, mainly through the use of low molecular weight heparin and a multidisciplinary care approach, significantly improve maternal and fetal outcomes. LMWH was associated with fewer complications compared to UFH, highlighting its effectiveness and safety in treating pregnant women with VTE.

The Efficacy and Safety of DOACs in Inherited Antithrombin Deficiency: A Cohort Study from a Tertiary Referral Center.

Individuals with inherited antithrombin deficiency (IATD) have a high risk of venous thromboembolism (VTE). Most VTEs are managed with direct oral anticoagulants (DOACs), but the utility of DOACs in antithrombin deficiency (ATD) is unreported. Patients with IATD treated with DOAC were identified from our institutions' IATD registry. We assessed patients' characteristics, ATD type, and initial VTE characteristics, thrombosis recurrence and bleeding rates. Thirty-three patients received DOACs for 73 (38.5-111.5) months (median (interquartile range)). Prior to taking DOACs, 12 (36%) patients had VTE recurrence: these occurred after anticoagulation was ceased (4), nonadherence to VKA prior to DOAC use (3), or during heparin use in pregnancy (5). There were no VTE recurrences on standard-dose DOAC, except in a noncompliant patient receiving dabigatran. There was one recurrence with compliant DOAC use-a patient receiving rivaroxaban 10 mg. Six (18%) patients experienced clinically relevant bleeding, which was predominantly menorrhagia (5/6). One major bleeding event, intracranial hemorrhage, occurred in a patient receiving full-dose rivaroxaban who had refractory hypertension (0.5 events/100 patient-years). In this cohort, compliant DOAC users had an overall VTE recurrence rate of 0.5/100 patient-years, whereas with low-dose DOACs the event rate was 3.5/100 patient-years. Standard-dose DOACs appear efficacious and relatively safe in IATD.

Recurrent venous thromboembolism and vaginal estradiol in women with prior venous thromboembolism: A nested case-control study.

Whether vaginal estradiol use is associated with an increased risk of recurrent venous thromboembolism (VTE) in women with prior VTE is unknown. We sought to evaluate the association between vaginal estradiol use and recurrent VTE in women with prior VTE. We performed a nationwide nested case-control study among 44 024 women aged ≥45 years who developed a first VTE without a history of vaginal estrogen use prior to VTE diagnosis. Cases with recurrent VTE were matched 1:2 on birth year with controls using incidence density sampling. Exposure to vaginal estradiol tablets was categorized into current use (0-2 months before index), prior use (2-24 months before index) and past use (more than 24 months prior to index). We identified 5066 cases and 10 127 age-matched controls. In fully adjusted analysis vaginal estrogen was not associated with recurrent VTE with a hazard ratio of 0.75, p = .07 for current use, 0.83, p = .13 for prior use, and 1.24, p = .06 for past use. Use of vaginal estradiol tablets in women with prior VTE was not associated with an increased rate of recurrent VTE. Our study indicates that vaginal estradiol therapy is unlikely to increase risk of recurrent VTE in women with prior VTE.

Effectiveness and Safety of Extended Treatment Apixaban Versus Low-Molecular-Weight Heparin in Cancer-Associated Venous Thromboembolism.

Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months. A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB). A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH. Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.

Venous thromboembolism in women with hormone-dependent breast cancer. To continue or discontinue hormonal treatment? Insights from the RIETE registry

IntroductionHormone therapy (HT) for breast cancer is associated with an increased risk of venous thromboembolism (VTE). This study examines the effects of continuing versus discontinuing HT on VTE recurrence, major bleeding, and mortality, after an acute VTE event. MethodsUsing data in the RIETE-registry from March 2001 through September 2021, we calculated incidence rates and rate-ratios (RR) for VTE events in patients on- and off HT. Cox regression models assessed the impact of HT continuation. ResultsAmong 479 women with breast cancer on HT who developed VTE (pulmonary embolism 279, isolated deep vein thrombosis 200), 350 (73 %) continued HT. These women were slightly older (70 ± 13 vs. 67 ± 16 years) than those discontinuing HT, with no significant differences in other baseline characteristics. Over a median follow-up of 294 days, 25 (5.2 %) developed VTE recurrences, 18 (3.7 %) had major bleeding, and 73 (15.2 %) died. Rates of VTE recurrence did not differ significantly between groups (RR: 1.28, 95 % CI 0.44–3.75), except in the first three months post-VTE, where a higher rate was observed in those continuing HT (6.02/100 patients-year vs. no events). On multivariable analysis, HT continuation showed no association with VTE recurrences after adjusting for other thromboembolic risk factors (adjusted hazard ratio [aHR] 1.49, 95 % CI 0.5–4.45). ConclusionContinuing HT after a VTE event in women with breast cancer does not generally affect the long-term risk of VTE recurrences but is associated with a higher risk in the first three months. These findings highlight the need for careful monitoring during this period.

Safety and efficacy of anticoagulant treatment in patients with ovarian vein thrombosis: a systematic review and meta-analysis of observational studies

BackgroundThe role of anticoagulation in ovarian vein thrombosis (OVT) is uncertain. ObjectivesWe aimed to evaluate safety and efficacy of anticoagulant treatment in OVT patients. MethodsA systematic search was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases up to April 2024. Eligible studies included randomized controlled trials and observational studies enrolling at least 10 adult patients with objectively diagnosed OVT and treated with any anticoagulants. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42021270883). ResultsWe included 17 observational studies (621 anticoagulated and 376 nonanticoagulated OVT patients); 9 studies enrolled mainly pregnancy/puerperium-related OVT. Most patients received heparins alone (45.7%) or proceeded to vitamin K antagonists (39.2%). The average treatment duration was ≤3 months in 8 studies (47.1%), >3 to ≤6 months in 6 studies (35.3%), and >6 months in 3 studies (17.6%). In treated patients, mortality rate was 2.43% (95% CI, 0.54%-5.41%; I2 = 53.8%; 12/406 patients; 13 studies), major bleeding was 1.27% (95% CI, 0.48%-2.38%; I2 = 2.5%; 7/583 patients; 15 studies), recurrent venous thromboembolism (VTE) was 3.49% (95% CI, 1.12%-6.95%; I2 = 63.5%; 22/482 patients; 15 studies), and vessel recanalization was 89.4% (95% CI, 74.6%-98.6%; I2 = 80.6%; 163/184 patients; 8 studies). The rate of recurrent VTE in untreated patients was 8.65% (95% CI, 2.61%-17.35%); however, the difference compared with treated patients was not statistically significant (risk ratio, 0.70; 95% CI, 0.36-1.37). At subgroup analyses, the rates of major bleeding and recurrent VTE were 0.80% (95% CI, 0.0-2%.17%) and 3.81% (95% CI, 0.42%-9.63%) in pregnancy/puerperium-related OVT, respectively, and 1.12% (95% CI, 0.32%-2.34%) and 1.78% (95% CI, 0.62%-3.46%), respectively, when analyzing only full-text studies. ConclusionThere is paucity of literature regarding OVT. Our results suggest that anticoagulation is associated with low rates of major bleeding and recurrent VTE.

Direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension patients: A retrospective cohort study

IntroductionDirect oral anticoagulants (DOACs) are increasingly prescribed for life-long anticoagulation in chronic thromboembolic pulmonary hypertension (CTEPH) patients, despite not being recommended in the guidelines. This study aims to evaluate the efficacy and safety of DOACs in CTEPH patients. MethodsFrom May 2013 to December 2022, patients who were first diagnosed with CTEPH in Fuwai Hospital and started long-term anticoagulation treatment with warfarin or DOACs were retrospectively included and followed up until (1) death, (2) transition to other kinds of anticoagulants, or (3) discontinuation of anticoagulation. Propensity score matching was used to balance confounding bias of baseline characteristics. All-cause death, major bleeding, clinically relevant nonmajor bleeding and venous thromboembolism (VTE) recurrence were obtained and analysed. ResultsAfter propensity score matching, 115 patients taking warfarin and 206 patients taking DOACs were included in our study and followed up for 5.5 [3.4, 7.1] years. There was no significant difference of survival between the warfarin and the DOAC group (p = 0.77). The exposure adjusted event rate of major bleeding (0.3 %/person-year vs 0.4 %/person-year, p = 0.705) and clinically relevant nonmajor bleeding (3.1 %/person-year vs 3.2 %/person-year, p > 0.999) was similar between two groups. The exposure adjusted rate of VTE recurrence was significantly higher in the DOAC group (1.5 %/person-year vs 0.3 %/person-year, p = 0.030). ConclusionIn anticoagulation of CTEPH patients, DOACs have similar survival rate, similar risk of bleeding but higher risk of VTE recurrence than warfarin.

Post-Discharge Treatment Patterns among Patients Treated with Apixaban or Warfarin during Hospitalization for Venous Thromboembolism (VTE).

Background: Oral anticoagulants (OACs), such as apixaban and warfarin, are indicated for reducing the risk of recurrent venous thromboembolism (VTE) and are often initiated in the hospital. The aim of this study was to evaluate OAC continuity from inpatient to outpatient settings and the risk of recurrent VTE among patients with an initial event. Methods: This retrospective cohort study utilized hospital charge data and medical and prescription claims from 1 July 2016 to 31 December 2022 to identify adults treated with apixaban or warfarin while hospitalized for VTE. Patients were followed to assess switching or discontinuation post-discharge and the risk of recurrent VTE. The index date was the date of the first apixaban or warfarin claim within 30 days post-discharge. Results: Of the 19,303 eligible patients hospitalized with VTE, 85% (n = 16,401) were treated with apixaban and 15% (n = 2902) received warfarin. After discharge, approximately 70% had ≥1 fill for their respective apixaban or warfarin therapy. The cumulative incidence of discontinuation over the 6 months following index was 50.5% and 52.2% for the apixaban and warfarin cohorts, respectively; the cumulative incidence of switching was 6.0% and 20.9%, respectively. The incidence rates of recurrent VTE were 1.2 and 2.5 per 100 person-years for the apixaban and warfarin cohorts, respectively. Conclusions: The majority of patients continued their apixaban or warfarin therapy following hospital discharge; however, a considerable proportion either switched or discontinued OAC upon transitioning from inpatient care. Among those who continued therapy, discontinuation, switch, and recurrent VTE occurred less often with apixaban vs. warfarin.

A retrospective review of recurrent venous thromboembolism in patients with cancer with direct factor Xa inhibitors.

e24136 Background: Venous thromboembolism (VTE) in cancer patients is a significant cause of morbidity and mortality. People with malignancies are at an increased risk of thrombosis compared to the normal population. Regimens that include platinum-based agents and vascular endothelial growth factor (VEGF) inhibitors have a higher risk of thromboembolism1. The recent ASCO 2023 guidelines for VTE prophylaxis and treatment have advised that direct factor Xa inhibitors are a suitable option for initial and long-term treatment for VTE, given patient preference of oral over subcutaneous administration of anti coagulation2. In our retrospective review of a single centre in Western Australia, we have identified twelve patients who have developed thromboembolic events whilst on direct oral anticoagulation. Methods: Electronic patient records were reviewed for oncology patients attending between 2016 and 2023 at a single centre in Western Australia.Diagnosis of VTE and subsequent treatment was confirmed from radiology and medication records. Twelve patients were identified, and data was recorded and analysed. Results: 12 patients were identified with recurrent VTE whilst on direct factor Xa inhibitors. The median age was 59.5 years (range 50-71). The most common associated malignancies were pancreatic, ovarian and lung cancer. Others include breast, vulval, colon and gastroesophageal cancer. Two thirds of patients were metastatic at diagnosis (n = 8). Common sites of thrombosis include the lower limbs at both initial [n = 6] and recurrent [n = 4] presentation. All patients were treated with therapeutic doses of rivaroxaban (n = 8) or apixaban (n = 4) at the time of of initial or recurrent thrombotic event. Median time to initial thrombotic event was 4.5 months from diagnosis compared to recurrent VTE [5 months]. All patients were changed to either LMWH (n = 10) or unfractionated heparin (n = 2). Ten patients [83.3%] did not have further thrombosis post switching to heparin. One patient had recurrent pulmonary emboli on imaging despite heparin administration, and the other had an IVC filter insertion. Conclusions: VTE is a common complication for oncology patients. Given our results, clinicians should be suspicious for recurrent VTE for patients on direct factor Xa inhibitors. There is an argument for enoxaparin or dalteparin to be better options, particularly in those high risk. Whilst patient preference for an oral option is desirable, further investigation is needed to directly compare the differing direct factor Xa inhibitors and the rates of VTE recurrence.

Safety and efficacy of low-molecular-weight heparin in patients with acute venous thromboembolism postthrombolytic therapy as compared to unfractionated heparin: A systematic review and meta-analysis

Abstract: BACKGROUND: Low-molecular-weight heparin (LMWH) is a proven treatment for patients with venous thromboembolism (VTE) with a lower risk of VTE recurrence and lower rates of major hemorrhage compared to unfractionated heparin (UFH) and have largely replaced its use in many indications, but its use around thrombolysis remains controversial. AIM: This study aims to evaluate the currently available evidence on LMWH use in postthrombolysis as compared to UFH. MATERIALS AND METHODS: Embase and MEDLINE were searched between 1992 and 2022, in addition to other sources. We included experimental and observational studies that assessed the use of LMWH as compared to UFH in patients with massive and submissive pulmonary embolism (PE) in the acute postthrombolysis phase. Data were pooled to estimate odds ratios (ORs), with 95% confidence intervals for VTE recurrence, bleeding complications and 30-day mortality. RESULTS: Three studies were included in this systematic review: one randomized controlled trial, one prospective, and one retrospective study. A total of 299 patients were treated with UFH, and 227 patients were treated with LMWH. Patients treated with LMWH had a statistically significant lower risk of major bleeding with OR 0.41 (0.17, 0.97) P = 0.04 and 30-day mortality with OR 0.44 (0.23, 0.85) P = 0.01. On the other hand, though the risk of VTE recurrence and clinically relevant non-major bleeding (CRNMB) were lower, this was not statistically significant with OR of 0.18 (0.03, 1.07) P = 0.06 for VTE recurrence, and OR of 0.75 (0.39, 1.42) P = 0.38 for CRNMB. CONCLUSION: In patients with massive and submissive PE postthrombolysis, LMWH is a reasonable option for anticoagulation with lower risk of VTE recurrence, bleeding complications and 30-day mortality when compared to UFH. However, this conclusion is largely influenced by observational data and the very limited evidence available. Certainly, more studies are needed to evaluate this clinical question.

Risk of recurrence after discontinuing anticoagulation in patients with COVID-19- associated venous thromboembolism: a prospective multicentre cohort study

The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences. In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Sanofi and Rovi, Sanofi Spain.

Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism

BackgroundThe duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding. ObjectivesAnalyze rates and case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation. MethodsWe compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding. ResultsOf 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio [HR], 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding. ConclusionRecurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these outcomes.

Venous thromboembolism characteristics and outcomes among RIETE patients tested and untested for inherited thrombophilia

AbstractInherited thrombophilia (IT) workup is commonly pursued in patients with venous thromboembolism (VTE). Recent American Society of Hematology guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large, prospective Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were analyzed to compare VTE risk factors, management, and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and after its discontinuation. Among 103 818 patients enrolled in RIETE, 21 089 (20.3%) were tested for IT, 8422 (8.1%) tested positive, and 82 729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors and less common in those with major risk factors such as surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However, IT-negative patients with pregnancy or postpartum-related VTE had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates after treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities. The trial was registered at www.clinicaltrials.gov as #NCT02832245.

Outcomes of venous thromboembolism in patients with inherited thrombophilia treated with direct oral anticoagulants: insights from the RIETE registry.

While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39.9%) tested positive: Protein C deficiency 294, Protein S deficiency 726, Antithrombin deficiency 240, Factor V Leiden 2248, Prothrombin gene mutation 1434, combined IT 3480. Overall, 14,189 RIETE patients (6.2% with IT) received DOACs, and 89,629 standard anticoagulation (8.4% with IT), mostly with heparins followed by vitamin K antagonists. Proportions of patients receiving DOACs did not differ between IT-positive and IT-negative patients. Rates of VTE recurrence on anticoagulant treatment were highest in patients with AT deficiency (P < 0.01). Rates of on-treatment major bleeding and all-cause mortality were lowest among patients with Factor V Leiden (FVL) or PT G20210A mutations, compared with patients who tested negative. Patients with IT who received DOACs had lower rates of major bleeding than those receiving standard anticoagulation. Excluding FVL and Protein S deficiency, patients with IT had lower rates of VTE recurrence with DOACs than with standard anticoagulation. DOACs are equally safe and effective in VTE patients with IT, with lower bleeding rates than those on standard anticoagulation.

The Role of Hereditary Thrombophilia Testing in Management of First-Time Pulmonary Embolism

Hereditary thrombophilia (HT) testing is frequently conducted during the evaluation of patients with pulmonary embolism (PE). However, the utility of routine HT testing in this setting is unclear. We sought to assess the association of HT with risk of recurrent venous thromboembolism (VTE) following first-time PE. We conducted a multi-hospital retrospective study. Two hundred and ninety (290) patients with a first-time PE, who had been tested for HT, completed at least 3 months of therapeutic anticoagulation (AC), subsequently discontinued AC, and were followed for at least 36 months thereafter, were included. HT was present in 48 of the 290 included patients (17%). Median follow-up after discontinuing AC was 61 months (interquartile range, 43-79 months). The overall recurrence rate of VTE during follow-up was 58 per 290 (20%). A total of 47 of 242 patients (19%) in the HT-absent group had a recurrent VTE, compared with 11 of 48 (22%) in the HT-present group. There was no significant difference in VTE-free survival between groups on Kaplan-Meier analysis; the hazard ratio (HR) for VTE recurrence for those with HT compared to those without (HR HT-present: HT-absent) was 1.240 (95% confidence interval [CI] 0.614-2.502; p=0.548). On multivariable analysis, HT was not associated with risk of recurrent VTE (HR 1.262; 95% CI 0.640-2.488), and the only variable associated with VTE recurrence was unprovoked PE (HR 2.954; 95% CI 1.64-5.314). These findings demonstrate that the presence of HT is not associated with the risk of recurrent VTE following first PE, and support limiting the use of HT testing among patients with first PE.