Cancer-associated Venous Thromboembolism Research Articles

Efficacy and safety of novel oral anticoagulants for the treatment of cancer-associated venous thromboembolism: protocol for an umbrella review of systematic reviews and meta-analyses

IntroductionNovel oral anticoagulants (NOACs) have been used in antithrombotic therapy in patients with cancer, and their efficacy and safety have been evaluated in several meta-analyses. Although a large body of...

An Update in Anticoagulant Therapy for Patients with Cancer-Associated Venous Thromboembolism.

This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion. Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient.

Cancer-Associated Thrombosis: A Taiwanese Perspective on Therapeutic Options with Focus on Non-Vitamin K Antagonist Oral Anticoagulants.

Cancer-associated thrombosis (CAT) is a common complication of malignancies. Patients with CAT are at risk of venous thromboembolism recurrence, but also at risk of bleeding while anticoagulated. Taiwanese patients are perceived to have a lower incidence of CAT, likely leading to false reassurance for Taiwanese patients with cancer. Because of this, oncologists and cardiologists from multiple medical institutions in Taiwan have set forth to provide clinical consensus guidelines on the management of CAT, based on local clinical practices and guided by predominant international clinical practice guidelines. This paper aims to describe the current disease burden of cancer-associated venous thromboembolism in Taiwanese cancer patients, and discusses the unmet needs and gaps in the management of this medical complication. It also outlines diagnostic and management strategies relevant to the different treatment options available, such as non-vitamin K antagonist oral anticoagulants.

Joint 2022 European Society of Thoracic Surgeons and The American Association for Thoracic Surgery guidelines for the prevention of cancer-associated venous thromboembolism in thoracic surgery.

Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a potentially fatal but preventable postoperative complication. Thoracic oncology patients undergoing surgical resection, often after multimodality induction therapy, represent among the highest risk groups for postoperative VTE. Currently there are no VTE prophylaxis guidelines specific to these thoracic surgery patients. Evidenced-based recommendations will help clinicians manage and mitigate risk of VTE in the postoperative period and inform best practice. These joint evidence-based guidelines from The American Association for Thoracic Surgery and the European Society of Thoracic Surgeons aim to inform clinicians and patients in decisions about prophylaxis to prevent VTE in patients undergoing surgical resection for lung or esophageal cancer. The American Association for Thoracic Surgery and the European Society of Thoracic Surgeons formed a multidisciplinary guideline panel that included broad membership to minimize potential bias when formulating recommendations. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment. The panel agreed on 24 recommendations focused on pharmacological and mechanical methods for prophylaxis in patients undergoing lobectomy and segmentectomy, pneumonectomy, and esophagectomy, as well as extended resections for lung cancer. The certainty of the supporting evidence for the majority of recommendations was judged as low or very low, largely due to a lack of direct evidence for thoracic surgery. The panel made conditional recommendations for use of parenteral anticoagulation for VTE prevention, in combination with mechanical methods, over no prophylaxis for cancer patients undergoing anatomic lung resection or esophagectomy. Other key recommendations include: conditional recommendations for using parenteral anticoagulants over direct oral anticoagulants, with use of direct oral anticoagulants suggested only in the context of clinical trials; conditional recommendation for using extended prophylaxis for 28 to 35days over in-hospital prophylaxis only for patients at moderate or high risk of thrombosis; and conditional recommendations for VTE screening in patients undergoing pneumonectomy and esophagectomy. Future research priorities include the role of preoperative thromboprophylaxis and the role of risk stratification to guide use of extended prophylaxis.

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis

Recurrent Thrombosis and Bleeding in Patients with Cancer-Associated Venous Thromboembolism Receiving Anticoagulation: Are These Modifiable Risk Factors for Mortality?

Patients with cancer associated venous thromboembolism (VTE) have a higher risk of recurrent VTE than those without cancer and require long-term anticoagulation, but these patients are also at higher risk of anticoagulant-related bleeding because of the frequent presence of disease- or treatment-related predispositions for bleeding.

Risk factors for recurrence and major bleeding in patients with cancer-associated venous thromboembolism

Risks of recurrence and treatment-emergent bleeding are high in patients with cancer-associated venous thromboembolism (VTE) but factors associated with these risks remain substantially undefined.The aim of this analysis in patients with cancer-associated VTE included in the Caravaggio study was to identify risk factors for recurrent VTE and major bleeding. Variables potentially predictive for recurrent VTE or major bleeding were evaluated in a Cox proportional hazard multivariable analysis with backward variable selection.Recurrent VTE occurred in 78 patients (6.8%) and major bleeding in 45 (3.9%). Independent risk factors for recurrent VTE were deep vein thrombosis (DVT) as index event (Hazard ratio (HR) 1.84, 95% CI 1.17–2.88), ECOG status of 1 or more (HR 1.95, 95% CI 1.11–3.43), pancreatic or hepatobiliary cancer site (HR 2.20, 95% CI 1.19–4.06), concomitant anti-cancer treatment (HR 1.98, 95% CI 1.03–3.81) and creatinine clearance (HR 1.10, 95% CI 1.00–1.20 for every 10 ml/min absolute increase). Independent risk factors for major bleeding were ECOG status of 2 (HR 2.31, 95% CI 1.24–4.29), genitourinary cancer site (HR 2.72, 95% CI 1.28–5.77), upper gastrointestinal cancer site (HR 3.17, 95% CI 1.22–8.23), and non-resected luminal gastrointestinal cancer (HR 2.77, 95% CI 1.38–5.56).This analysis of the Caravaggio study in patients with cancer-associated VTE who were on standardized anticoagulant treatment identified five independent predictors for recurrent VTE and four independent predictors of treatment-emergent major bleeding. Considering these risks could help clinicians to optimize the anticoagulant treatment in patients with cancer-associated VTE.

Comparison of the efficacy and safety of rivaroxaban and low-molecular-weight heparin in Chinese lung cancer patients with nonhigh-risk pulmonary embolism

BackgroundData that guide selection of differing anticoagulant regimens for specific cancer-associated venous thromboembolism (VTE) are lacking. We aimed to compare the efficacy and safety of rivaroxaban and low-molecular-weight heparin (LMWH) against nonhigh-risk pulmonary embolism (PE) in Chinese lung cancer patients.MethodsFour hundred forty-six Chinese lung cancer patients with nonhigh-risk PE who initiated treatment with rivaroxaban or LMWH were identified from Zhongshan Hospital database from 2016 to 2020. The primary outcomes were the composite event of VTE recurrence or major bleeding, and all-cause mortality. The secondary outcomes were VTE recurrence, major bleeding and clinically relevant non-major bleeding (CRNMB). Propensity score matching was used to balance baseline covariates. We conducted sensitivity analysis by stabilized inverse probability of treatment weighting and competing risk analysis by a Fine and Gray subdistribution hazard model.ResultsIn propensity score-matched cohorts, rivaroxaban was similar to LMWH in the risks of the composite outcome (hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.45–1.21; P = 0.22), VTE recurrence (HR, 0.69; 95% CI, 0.36–1.34; P = 0.28), major bleeding (HR, 0.79; 95% CI, 0.37–1.68; P = 0.54) and CRNMB (HR, 1.13; 95% CI, 0.62–2.09; P = 0.69). All-cause mortality was significantly lower in rivaroxaban group than LMWH group (HR, 0.52; 95% CI, 0.36–0.75; P < 0.001). The primary and secondary outcomes favored rivaroxaban over LMWH in all the subgroups expect for central PE and intermediate-risk PE. The sensitivity analysis yielded similar results, and competing risk analysis was in accordance with the primary findings.ConclusionsRivaroxaban might be a promising alternative to LMWH as initial treatment for nonhigh-risk PE in lung cancer patients.

A Clinical-Genetic Risk Score for Predicting Cancer-Associated Venous Thromboembolism: A Development and Validation Study Involving Two Independent Prospective Cohorts.

Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. The Khorana score was developed for assessing the risk of VTE in outpatients with cancer receiving chemotherapy, but its accuracy in identifying patients at high risk has been questioned. The aim of this study was to develop and validate a clinical-genetic score that improves the assessment of VTE risk in oncology outpatients within 6 months of diagnosis. The new score was developed using the data of 364 outpatients belonging to the Spanish ONCOTHROMB 12-01 population. In this cohort, clinical data associated with the risk of VTE were collected at the time of diagnosis, including the Khorana score. These patients were also genotyped for the 51 genetic variants known to be associated with VTE. Multivariate logistic regression was performed to determine the weight of each genetic and clinical variable in relation to VTE risk, allowing a clinical-genetic risk score (the ONCOTHROMB score) to be developed. The Khorana and the ONCOTHROMB scores were then compared via the area under the receiver operating characteristic curve (AUC), calibration, and the number of patients needed to treat. The new score was then validated in a study of 263 patients in the Vienna Cancer and Thrombosis Study population. Nine genetic variants, tumor site, TNM stage, and a body mass index of > 25 kg/m2 were found to be associated with VTE and were used to build the ONCOTHROMB score, which better predicted the overall risk of VTE than did the Khorana score (AUC, 0.781 v 0.580; P < .001). Similar AUC results were recorded in the validation study the Vienna Cancer and Thrombosis Study cohort involving patients with the same type of tumor (AUC for the ONCOTHROMB score v the Khorana score: 0.686 v 0.577; P < .001) and with all type of tumors (AUC for the ONCOTHROMB score v the Khorana score: 0.720 v 0.561; P < .0001). The ONCOTHROMB score for VTE risk in outpatients with cancer, which takes into account both clinical and genetic variables, better identifies patients who might benefit from primary thromboprophylaxis than does the Khorana score.

Survey of medical oncologists and trainee practice on venous thromboembolism prophylaxis and treatment in solid cancers.

Venous thromboembolism (VTE) has a significant adverse impact on the outcomes of patients with active solid malignancies. Prophylaxis is indicated for cancer-associated VTE (CA-VTE) using the Khorana score for risk stratification. We surveyed medical oncology fellows and trainees regarding their practice in CA-VTE. Regarding treatment of CA-VTE, practice was consistent with guidelines. However, regarding prophylaxis for CA-VTE, there was a high degree of uncertainty, which highlights theneed for ongoing education.

Treatment and prevention of cancer-associated thrombosis in the Netherlands: A national survey

BackgroundIn the recent years, numerous studies on the optimal treatment and prevention of cancer-associated venous thromboembolism (VTE) have been published, leading to updated (inter)national guidelines. These include direct oral anticoagulants (DOACs) as the first-line treatment agent in general and the recommendation of primary thromboprophylaxis in selected ambulatory patients. ObjectivesThe objective of this study was to evaluate the clinical practice regarding treatment and prevention of VTE in patients with cancer in the Netherlands and practice variation among different specialties. MethodsAn online survey was conducted between December 2021, and June 2022, among Dutch physicians (oncologists, hematologists, vascular medicine specialists, acute internal medicine specialists, and pulmonologists) treating patients with cancer, in which we explored the treatment of choice for cancer-associated VTE, the use of VTE risk stratification tools, and primary thromboprophylaxis. ResultsA total of 222 physicians participated, of whom the majority (81%) used DOACs as a first-line agent for treating cancer-associated VTE. The treatment varied between the following specialties: hematologists and acute internal medicine specialists more often prescribed low-molecular-weight heparin than physicians of the other specialties (OR, 0.32; 95% CI, 0.13-0.80). The minimum duration of anticoagulant treatment was usually 3 to 6 months (87%), and treatment was extended when the malignancy was still active (98%). Regarding the prevention of cancer-associated VTE, no risk stratification tool was used. Three quarters of respondents never prescribed thromboprophylaxis to ambulatory patients, mostly because the thrombosis risk was not perceived high enough to justify prophylaxis. ConclusionDutch physicians largely adhere to the updated guidelines regarding the treatment of cancer-associated VTE but less to the recommendations for its prevention.

High D-Dimer Level at First Incident Cancer-Associated Venous Thromboembolism is a Predictor for Recurrence

BACKGROUND: Cancer is considered a major risk factor of venous thromboembolism (VTE). Whether the D-dimer level at first incident cancer-associated VTE can predict recurrence is not fully elucidated. AIM: The aim of this study was to assess the association between D-dimer level measured at first incident cancer-associated VTE and risk of recurrence. METHODS: In this study, the electronic records of all patients with first incident cancer-associated VTE were retrospectively retrieved and followed up for a period of 36 months. The measured levels of D-dimer and clinical predictors for each patient prior intervention were collected. Univariate and multivariant Cox regressions were fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 73 (34.3%) of 213 cancer-associated VTE patients had recurrent VTE. The crude recurrence rate was 11.4/100 person-years (95% CI, 9.2–14.2). The mean value of D-dimer was significantly higher seen in recurrent VTE patients than those without recurrence (14.8 ± 7.5 mg/L vs. 4.8 ± 5.7 mg/L, P &lt; 0.001). The highest positive likelihood ratio using area under the receiver operating characteristic (ROC) curve occurred when a D-dimer threshold of 8.67 mg/L was chosen. At this threshold, the D-dimer was 92% sensitive and 80% specific in predicting recurrent VTE. The area under the ROC curve was 0.924 (95% CI 0.887–0.960, P &lt; 0.001). Patients with a D-dimer ≥8.67 mg/L at first VTE in our study were 3.1-fold more likely to have a recurrence than those with lower D-dimer results. CONCLUSION: A D-dimer ≥8.67 mg/L measured at the first incident cancer-associated VTE was associated with a 3.1-fold increased hazard of recurrence events. Our finding suggests that a low D-dimer level at the time of first cancer-associated VTE is suitable in the clinical practice to avoid extended-duration anticoagulation.

Rivaroxaban Versus Low-Molecular-Weight Heparins in a Broad Cohort of Patients With Cancer-Associated Venous Thromboembolism: An Analysis of the OSCAR-US Program.

Cancer-associated venous thromboembolism (CAT) guidelines recommend direct oral anticoagulants as alternatives to low-molecular-weight heparin (LMWH) in most patients. This study compared the effectiveness and safety of rivaroxaban versus LMWH for a broad CAT cohort. The cohort study used electronic health data from January 2012 to December 2020 to evaluate patients with active cancer experiencing acute venous thromboembolism (VTE) and treated with rivaroxaban or LMWH. Propensity score-overlap weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE, bleeding-related hospitalization, and all-cause mortality were calculated. In total, 4935 patients were identified (27.9% on rivaroxaban and 72.1% on LMWH). The cancer types included gastrointestinal (29.4%), genitourinary (26.2%), lung (24.0%), breast (19.7%), and hematologic (14.4%). Rivaroxaban was associated with a reduction in recurrent VTE versus LMWH among all patients with cancer (HR = 0.78; 95%CI = 0.61-0.99) at 3 months. No differences in bleeding-related hospitalization or all-cause mortality were observed. Directionally similar results to those at 3 months were observed at 6 months for all outcomes. In conclusion, we observed fewer recurrent VTE cases and no increase in bleeding-related hospitalizations with rivaroxaban versus LMWH at 3 months in this patient cohort with various cancer types.

Soluble P-selectin level in patients with cancer-associated venous and artery thromboembolism: a systematic review and meta-analysis

Soluble P-selectin level in patients with cancer-associated venous and artery thromboembolism: a systematic review and meta-analysis

Stratification of Risk Factors of Lung Cancer-Associated Venous Thromboembolism and Determining the Critical Point for Preemptive Intervention: A Systematic Review With Meta-analysis.

Several biomarkers or risk factors have been identified and several prediction models exist. The major limitations inherent in these models include cost-ineffectiveness and lack of systematic stratification of risk factors resulting in the inclusion of clinically insignificant biomarkers in the models. This review aimed to systematically stratify the risk factors of lung cancer-associated venous thromboembolism (VTE) and determine the critical point for preemptive intervention. This systematic review was structured as per the Preferred Reporting Item for Systematic Reviews and Meta-analyses. We searched MEDLINE, PubMed, Cochrane Library, CINAHL, Academic Search Complete, and PsycINFO from the onset to June 2022. We included studies that reported the risk factors of lung cancer-associated VTE and corresponding risk estimates, irrespective of treatment status but studies were excluded if patients were on anti-VTE medications. We employed random effects models of meta-analysis and computed risk stability index and risk weight (Rw) to achieve the review objectives. The review protocol is registered with PROSPERO (CRD42022336476). The clinically significant risk factors of VTE in lung cancer patients were D-dimer (odds ratio [OR] = 5.510, 95% CI = 2.6-11.7; Rw = 5.0), albumin (OR = 2.2, 95% CI = 1.0-4.8; Rw = 1.79), leukocyte (OR = 2.48, 95% CI = 1.9-3.2; Rw = 1.77), histological type (OR = 1.69 , 95% CI = 1.2-2.4; Rw = 1.3), age (OR = 1.56; Rw = 0.99), and hemoglobin (OR = 1.85, 95% CI = 1.3-2.6; Rw = 0.92). Based on the distribution of Rw across risk factors, the critical point (upper third of the upper quartile class) was 4.5 and may mark the point at which preemptive intervention should be commenced. Targeted screening for VTE in lung cancer patients could be patient-specific and should be based on a combination of the most significant risk factors required to meet the critical point, provided that such a combination is affordable as illustrated in the ALBAH model. The review protocol is registered with PROSPERO (ID: CRD42022336476).

Management of cancer-associated thrombosis—current status of treatment of cancer-associated venous thromboembolism—

Management of cancer-associated thrombosis—current status of treatment of cancer-associated venous thromboembolism—

Machine learning predicts cancer-associated venous thromboembolism using clinically available variables in gastric cancer patients

Stomach cancer (GC) has one of the highest rates of thrombosis among cancers and can lead to considerable morbidity, mortality, and additional costs. However, to date, there is no suitable venous thromboembolism (VTE) prediction model for gastric cancer patients to predict risk. Therefore, there is an urgent need to establish a clinical prediction model for VTE in gastric cancer patients. We collected data on 3092 patients between January 1, 2018 and December 31, 2021. And after feature selection, 11 variables are reserved as predictors to build the model. Five machine learning (ML) algorithms are used to build different VTE predictive models. The accuracy, sensitivity, specificity, and AUC of these five models were compared with traditional logistic regression (LR) to recommend the best VTE prediction model. RF and XGB models have selected the essential characters in the model: Clinical stage, Blood Transfusion History, D-Dimer, AGE, and FDP. The model has an AUC of 0.825, an accuracy of 0.799, a sensitivity of 0.710, and a specificity of 0.802 in the validation set. The model has good performance and high application value in clinical practice, and can identify high-risk groups of gastric cancer patients and prevent venous thromboembolism.

DOAC in the treatment of cancer-associated venous thromboembolism: a retrospective cohort study beyond the guidelines

BackgroundThe emerging use of direct oral anticoagulants (DOAC) in the management of cancer-associated venous thromboembolism (CAT) is significantly improving therapeutic adherence and quality of life. Despite this, many conditions can restrict the therapeutic index of these drugs. For all these reasons the latest guidelines recommend the use of heparins in the treatment of CAT as the preferred treatment in some clinical settings.ObjectivesWe evaluated the efficacy and the safety of DOAC, in terms of recurrent venous thromboembolism (VTE) and major bleeding (MB), as a composite primary outcome. Mortality and clinically relevant non-major bleeding (CRNMB) were evaluated as secondary outcomes.MethodsWe performed a retrospective study on 209 patients to compare the effects of DOAC versus heparins for the treatment of CAT. 127 patients with a high bleeding risk neoplasia were enrolled.ResultsA primary-outcome event occurred in 11.3% of patients treated with heparins and in 10.5% treated with DOAC (Relative Risk 0.92; 95% CI 0.42–2.01, p = 0.84). Recurrent VTE occurred in 6.1% in the heparins group and in 8.4% in the DOAC group (RR 1.37; 95% CI 0.51–3.64, p = 0.52). MB occurred in 5.2% in the heparins group and in 2.1% in the DOAC group (RR 0.40; 95% CI 0.08–1.93, p = 0.25).ConclusionsDOAC seem to be as effective and safe as heparins in the treatment of CAT. Most bleeding events occurred in patients with high-risk bleeding neoplasms regardless of the type of anticoagulant. Considering the characteristics and satisfaction of patients using DOAC in this setting, this approach should be considered as a first choice.

Survival Implications of Thrombus Recurrence or Bleeding in Cancer Patients Receiving Anticoagulation for Venous Thromboembolism Treatment.

Study aims were to analyze prospectively collected data from patients with cancer-associated venous thromboembolism (VTE) to determine the impact of VTE recurrence and anticoagulant-related bleeding on all-cause mortality. Consecutive cancer patients with acute VTE treated with anticoagulants (March 1, 2013-November 30, 2021) were included in this analysis. Anticoagulant therapy-associated VTE recurrences, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were assessed for their impact on all-cause mortality outcomes. This study included 1,812 cancer patients with VTE. Of these, there were 97 (5.4%) with recurrent VTE, 98 (5.4%) with major, and 104 (5.7%) with CRNMB while receiving anticoagulants. Recurrent VTE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.16-2.00; p = 0.0028), major bleeding (HR: 1.82; 95% CI: 1.41-2.31; p = 0.006), and CRNMB (HR; 1.38; 95% CI: 1.05-1.81; p = 0.018) each adversely influenced mortality outcomes. Deep vein thrombosis as the incident thrombotic event type was associated with VTE recurrence (HR: 1.78; 95% CI: 1.08-2.89; p = 0.02). Neither cancer type nor stage, chemotherapy, or Ottawa risk category influenced VTE recurrence. Higher body weights (HR: 1.01; 95% CI: 1.00-1.01; p = 0.005) were associated with increased major bleeding, while high Ottawa scores (HR: 0.66; 95% CI: 0.46-0.96; p = 0.03) and apixaban treatment (HR: 0.62; 95% CI: 0.45-0.84; p = 0.002) were associated with fewer major bleeding outcomes. Among cancer patients receiving anticoagulant therapy for VTE, adverse outcomes such as VTE recurrence, major bleeding, or CRNMB increase mortality risk by 40 to 80%. Identifying variables predicting these outcomes may help risk-stratify patients with poor prognosis.

Clot-regression effects of rivaroxaban in venous thromboembolism treatment in cancer patients—a prospective interventional study

Rivaroxaban, a direct oral anticoagulant, is effective against venous thromboembolism (VTE) recurrence without increasing the risk of major bleeding in patients with cancer-associated venous thromboembolism (CAT). However, its clot regression effects are poorly understood. This single-arm, prospective interventional study aimed to investigate the clot regression effects of rivaroxaban in 40 CAT patients, through a contrast-enhanced computed tomography at baseline, 3 weeks, and 3 months of rivaroxaban treatment. The primary endpoint was the clot-regression ratio calculated from the thrombus volumes at 3 weeks and 3 months. Compared with baseline, the total clot volume was significantly reduced at both 3 weeks and 3 months after initiation (p < 0.01). The clot-regression rates were statistically significant with 83.1% (95% confidence interval [CI], 73.8–92.3%) at 3 weeks and 98.7% (95% CI, 97.1–100.2%) at 3 months, with complete resolution in 36.1% and 80.8% of patients at 3 weeks and 3 months, respectively. One patient had recurrent VTE after dose reduction, and seven had non-fatal major bleeding. Therefore, rivaroxaban had a sufficient clot-regression effect against CAT with caution of bleeding complication.