Recurrent Intracranial Hemorrhage and Venous Thromboembolism Following Initial Intracranial Hemorrhage in Patients with Brain Tumors on Anticoagulation

Summary of key recommendations • VC filters are indicated to prevent pulmonary embolus(PE) in patients with venous thromboembolism (VTE)who have a contraindication to anticoagulation (grade B,level III).• Anticoagulation should be considered in patients with aVC filter when a temporary contraindication to antico-agulant therapy is no longer present. Insufficient dataexists to support a recommendation that all filter recip-ients should be treated with indefinite anticoagulationregardless of their risk of recurrent thrombosis (grade C,level IV). The decision as to whether or not to introduceanticoagulant therapy should be based on the perceivedunderlying thrombotic risk of the condition and thelikelihood of anticoagulant therapy-related bleeding.• VC filters are not indicated in unselected patients withVTE who will receive conventional anticoagulant therapy(grade A, level Ib).• VC filter insertion may be considered in selected patientswith PE despite therapeutic anticoagulation. Alternativetreatment options, such as long-term high-intensity oralanticoagulant therapy [international normalised ratio(INR) target 3AE5] or low molecular weight heparin(LMWH), should be considered prior to VC filterplacement, particularly in patients with thrombophilicdisorders (e.g. antiphospholipid syndrome) or cancer(grade C, level IV).• VC filter insertion may be considered in pregnantpatients who have contraindications to anticoagulationor develop extensive VTE shortly before delivery (within2 weeks). Retrievable filters should be considered (gradeC, level IV).• Free-floating thrombus is not an indication for insertionof a VC filter (grade B, level III).• Thrombolysis is not an indication for filter insertion. If afilter is used a retrievable filter should be used if available(grade C, level IV).• VC filters should be considered in any pre-operativepatient with recent VTE (within 1 month) in whomanticoagulation must be interrupted. Retrievable VCfilters should be considered in this situation where atemporary contraindication to anticoagulation exists(grade C, level IV).• No particular filter appears superior to others. Removablefilters should be used, if available, for patients with ashort-term contraindication to anticoagulant therapy(e.g. approximately 2 weeks) (grade C, level IV).

Outcomes of Low-Molecular-Weight Heparintreatment for Venous Thromboembolism in Patients with Primary and Metastatic Brain Tumors

Temporary and Permanent Inferior Vena Cava Filters in the Oncology Population

Background/Introduction Cancer is a strong risk factor for the development of venous thromboembolism (VTE) including pulmonary embolism (PE) and deep vein thrombosis (DVT). Patients with VTE have a long-term risk of recurrence, which can be prevented by anticoagulation therapy. Prolonged anticoagulation therapy is recommended for patients with cancer-associated VTE, although the risk of recurrence might depend on the individual patient. Purpose We aimed to identify the risk factors of recurrence in patients with cancer-associated VTE. Methods The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3027 consecutive patients with acute symptomatic VTE among 29 Japanese centers between January 2010 and August 2014. The present study population consisted of 695 cancer-associated VTE patients. The primary outcome measure in the present study was recurrent VTE, which was defined as PE and/or DVT with symptoms accompanied by confirmation of a new thrombus or exacerbation of the thrombus by objective imaging examinations or autopsy. Discontinuation of anticoagulation was defined as a withdrawal of anticoagulation therapy lasting >14 days for any reason. We selected clinically relevant variables and variables with P values <0.1 in a univariate analysis as potential risk factors, and constructed a multivariable Cox proportional hazard model for recurrent VTE incorporating the anticoagulation therapy status as a time-updated covariate. Results Among the 695 study patients, recurrent VTE occurred in 78 patients, of whom 54 (69%) occurred within 6 months. The cumulative incidence of recurrent VTE was 7.7% at 3-months, 8.9% at 6-months, 11.8% at 1-year, and 17.7% at 5-years. The cumulative incidence of discontinuation of anticoagulation therapy was 18.0% at 3-months, 29.5% at 6-months, 43.4% at 1-year, and 66.5% at 5-years. The cumulative 5-year incidence of recurrent VTE was most frequent in patients with uterus/ovary cancer (26.0%), followed by those with lung cancer (24.7%). The multivariable Cox proportional hazard model revealed that chronic kidney disease (HR, 2.27; 95% CI, 1.36–3.77, P=0.002), a high D-dimer level at the time of VTE diagnosis (HR, 2.85; 95% CI, 1.71–4.74, P<0.001), advanced cancer (HR, 1.69; 95% CI, 1.05–2.72, P=0.03) and discontinuation of anticoagulation therapy (HR, 2.66; 95% CI, 1.53–4.63, P<0.001) were independently associated with an increased risk of recurrent VTE. No cancer site was independently associated with an increased risk for recurrent VTE when adjusting for the above mentioned risk factors in the multivariable Cox proportional hazard model, although the risk of recurrent VTE numerically differed according to the cancer site. Conclusions Among patients with cancer-associated VTE, chronic kidney disease, a high D-dimer level at the time of VTE diagnosis, advanced cancer, and discontinuation of anticoagulation therapy were independent risk factors of recurrence. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation Figure 1Figure 2

Effectiveness and Safety of Rivaroxaban in Patients with Cancer-Associated Venous Thromboembolism

Utility of Inferior Vena Cava Filter in the Management of Venous Thromboembolism Among Patients with Brain Metastases: A Population-Based Study

Association of IVCF use with mortality and intracranial hemorrhage in patients with selected cancers and brain metastasis

Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin

In this study, we sought to investigate the effectiveness of inferior vena cava (IVC) filter placement in reducing the incidence of venous thromboembolism (VTE) in patients diagnosed with isolated calf deep vein thrombosis (DVT) after an intracranial hemorrhage or intracranial operation. A retrospective chart review (January 2000-December 2019) was performed to identify patients diagnosed with calf DVT after intracranial hemorrhage or intracranial operation. A total of 100 patients met the study criteria and were divided into groups based on treatment: IVC filter placement (n = 22), prophylactic anticoagulation (n = 42), or imaging surveillance (n = 36). Treatment-related complications were identified, and differences between groups in the primary endpoint (VTE occurrence after DVT diagnosis) were assessed using logistic regression. VTE occurred in 15 patients after calf DVT diagnosis. The rate of VTE was higher in the IVC filter group (9/22; 41%) than in the anticoagulation (2/42; 5%; p = 0.002) and surveillance (4/36; 11%; p = 0.013) groups. These treatment effects remained significant after adjustments were made for baseline characteristics (IVC filter vs anticoagulation, p = 0.009; IVC filter vs surveillance, p = 0.019). There was a single occurrence of pulmonary embolism in the surveillance group (3%). A single case of IVC filter thrombus was identified; no anticoagulation-related complications were reported. The findings of this study do not support IVC filter placement as a primary and solitary treatment for isolated calf DVT occurring after intracranial hemorrhage or intracranial operation.

Direct Oral Anticoagulants (DOACs) Vs. Low Molecular Weight Heparins (LMWH) for Venous Thromboembolism (VTE) in Patients with Primary Brain Tumors or Secondary Brain Metastases

Challenging anticoagulation cases: A case of pulmonary embolism shortly after spontaneous brain bleeding

Venous thromboembolism (VTE) is a common complication in cancer patients and anticoagulation (AC) remains the standard of care for treatment. Inferior vena cava (IVC) filters may also used to reduce the risk of pulmonary embolism, either alone or in addition to AC. Although widely used, data are limited on the safety and efficacy of IVC filters in cancer patients. We performed a retrospective review of outcomes after IVC filter insertion in a database of 1270 consecutive patients with cancer-associated pulmonary embolism (PE) at our institution between 2008 and 2009. Outcomes measured included rate of all recurrent VTE, recurrent PE, and overall survival within 12months. 317 (25%) of the 1270 patients with PE had IVC filters placed within 30days of the index PE event or prior to the index PE in the setting of prior DVT. Patients with IVC filters had markedly lower overall survival (7.3months) than the non-IVC filter patients (13.2months). Filter patients also had a lower rate of AC use at time of initial PE. There was a trend towards higher recurrent VTE in patients with IVC filters (11.9%) compared to non-filter patients (7.7%), but this was not significant (p = 0.086). The risk of recurrent PE was similar between the IVC filter cohort (3.5%) and non-filter group (3.5%, p = 0.99). Cancer patients receiving IVC filters had a similar risk of recurrent PE, but a trend towards more overall recurrent VTE. The filter patients had poorer overall survival, which may reflect a poorer cancer prognosis, and had greater contraindication to AC; therefore these patients likely had a higher inherent risk for recurrent VTE. A prospective study would be helpful for further clarification on the partial reduction in the recurrent PE risk by IVC filter placement in cancer patients.

Background In the direct oral anticoagulants (DOACs) era, extended anticoagulation after 6–12 months of treatment is an attractive strategy in patients with venous thromboembolism (VTE). Real-life data on the clinical benefit of DOAC over time is lacking. Purpose The aim of this study is to assess the effectiveness and safety of DOACs in patients with acute VTE treated for variable periods. Methods Data on patients with an objective diagnosis of acute VTE treated with DOACs were included in prospective cohort study. Study outcomes were recurrent VTE and major bleeding (ISTH definition). Results Overall, 934 patients were included (mean age 67.0±16.0, male gender 51.4%). Three-hundred and forty-six patients had a deep vein thrombosis (37.0%), 98 (10.5%) had isolated pulmonary embolism and 490 (52.5%) had both. One-hundred and sixty-nine patients (18.1%) had an active cancer, 59 (6.3%) a history of cancer and 365 patients (39.1%) an unprovoked VTE. During DOAC treatment (mean 21.6 months), 7 recurrent VTEs and 25 major bleedings occurred. In 546 and in 98 patients, DOAC was continued with full and reduced doses, respectively. In 290 patients (43.8% unprovoked, 13.8% active cancer, 42.4% associated with non-cancer risk factor), anticoagulants were withdrawn (average treatment duration 8.8 months) and 22 recurrent VTEs occurred over a follow-up off-treatment period of 31.9 months. In these patients, 2 episodes of major bleeding were observed. Overall, 201 patients died; fatal PE occurred in 4 and fatal bleeding in 1 patient. Time course for recurrent VTE according to 2019 ESC risk for recurrence is reported in the Figure. Conclusions In this cohort study, DOACs showed a good risk to benefit profile in the extended phase after an acute VTE event. Funding Acknowledgement Type of funding sources: None. Figure 1. Cumulative incidence of recurrent VTE

Intracranial hemorrhage (ICH) is the most feared and devastating complication of anticoagulant treatment, leading to death or disability in two thirds of cases. Once ICH occurs, the decision of whether to resume anticoagulation is a true therapeutic dilemma that requires balancing the competing risks of hematoma growth or recurrent ICH and disabling thromboembolic events. Although the risk of thromboembolism in patients off anticoagulation is higher than the overall risk of ICH recurrence, there is a marked paucity of prospective large population-based data on the real risk of ICH recurrence on warfarin. The lack of randomized controlled trials probably reflects the ethical challenge of prescribing patients a medication to which they have an apparent contraindication. Therefore, in clinical practice, the risk is usually, and inappropriately, extrapolated from the overall risk of major bleeding on warfarin (approximately 3%), in which older age and elevated international normalized ratio are factors associated with an increased risk. The little evidence available on resuming oral anticoagulation after ICH comes from either expert opinions or few nonrandomized mainly retrospective studies.1,2 These studies included highly selected high-risk patients and showed nonconclusive and even discrepant results. This limited and weak evidence along with our own …

Patient and operational factors that influence the decision to place an inferior vena cava filter in a pulmonary embolism response team