Cancer-related Venous Thromboembolism Research Articles

Open Issues in the Choice and Management of Direct Oral Anticoagulants in Patients with Cancer-Related Venous Thromboembolism.

Open Issues in the Choice and Management of Direct Oral Anticoagulants in Patients with Cancer-Related Venous Thromboembolism.

Risk of recurrent venous thromboembolism in cancer patients after discontinuation of anticoagulant therapy

Anticoagulant therapy is recommended for cancer-related venous thromboembolism (VTE). Recurrent VTE prevention is the main goal of this treatment. The majority of evidence-based practice guidelines recommend anticoagulant treatment for at least 6 months. Based on individual assessment of potential benefits and risks, tolerability, drug availability, patient preference, and cancer activity, active cancer patients should continue anticoagulant treatment beyond the 6-month course. When cancer is no longer active or the risk outweighs the benefit, anticoagulant therapy is usually stopped after 3-6 months. Until recently, there was little data on the risk of recurrent VTE in cancer-associated VTE patients after stopping anticoagulants. New results and evidence synthesis have emerged in the last 3 years. Recurring VTE occurs in over 30% in the 5 years after treatment discontinuation. In the first six months, recurrence rates are 10-15%. Recurrences reach 31% at 2 years and stabilize between 2 and 5. Duration of prior anticoagulation does not affect cumulative recurrence. The high risk of recurrent VTE after discontinuing treatment supports guidelines to continue anticoagulant treatment if cancer is active. Stopping anticoagulants after 3-6 months may not be ideal, so randomized clinical trials should be conducted quickly. This review highlights the need to improve cancer patients' primary VTE prevention efforts.

Assessment of patient characteristics in cancer-associated venous thrombosis in Türkiye (CAT-TR study)

Aim: In cancer patients, the overall risk of venous thromboembolism (VTE) is increased 7-fold, and in cases of certain malignancies, this risk increases to 28-fold. The main objectives of this study are to describe patterns of use of anticoagulants for the treatment of cancer-related VTE in Türkiye and to assess patient characteristics. Material and Methods: This was a multicenter, retrospective, descriptive study utilizing data from 17 centers across Türkiye. We included 2936 patients with a diagnosis of any cancer and a diagnosis of proximal lower-limb deep vein thrombosis (DVT) and/or pulmonary embolism (PE) between January 1, 2016, and December 31, 2019. These patients were only included if the cancer diagnosis was made at least 6 months before the diagnosis of VTE or within 30 days following the diagnosis of VTE. Patients were followed from the day after the index date until the earliest date among the dates of death, the end of the study, or the end of the 6-month treatment period. Results: The study included 2796 patients with VTE between 2016 and 2019. While 41.4% of the participants were female, 58.6% were male, and 66.1% of the patients had DVT while 45.2% had PE. Furthermore, 52.7% had a history of smoking and only three patients had known hereditary thrombophilia. Lung cancer was the most common type of cancer, diagnosed in 872 patients (29.3%), followed by colon cancer diagnosed in 255 patients (8.6%) and breast cancer diagnosed in 202 patients (6.8%). Among these patients, 70.3% were in an advanced stage of the disease. Chemotherapy was administered to 469 (65.7%) patients at the time of disease onset. Among the patients with VTE, 99.5% were treated, and low-molecular-weight heparin was used in 97.5% of these cases while 3% of the patients were treated with direct oral anticoagulants. Bleeding was observed in 1.6% of the patients who participated in this study, and 39.1% of the bleeding events whose type was specified were categorized as major bleeding. Bleeding was most intense in the gastrointestinal tract (56.7%). Recurrence was observed in 1.5% of the patients and improvement was observed in 42.1%. In the first 6 months after diagnosis, 14.3% of the patients died. Causes of mortality could not be obtained from the patients’ records. Conclusion: VTE is common in patients with active cancer and associated with high recurrence and mortality rates. Efforts are needed to prevent VTE, diagnose it in time, and reduce the recurrence rates, especially in the first year after VTE diagnosis.

Venous thromboembolism mortality and trends in older US adults, 2011-2019.

Venous thromboembolism (VTE) affects 1.2 million people per year in the United States. With several clinical changes in diagnosis and treatment approaches in the past decade, we evaluated contemporary post-VTE mortality risk profiles and trends. Incident VTE cases were identified from the 2011-2019 Medicare 20% Sample, which is representative of nearly all Americans aged 65 and older. The social deprivation index was linked from public data; race/ethnicity and sex were self-reported. The all-cause mortality risk 30 days and 1 year after incident VTE was calculated in demographic subgroups and by prevalent cancer diagnosis status using model-based standardization. Risks for major cancer types, risk differences by age, sex, race/ethnicity, and socio-economic status (SES), and trends over time are also reported. The all-cause mortality risk among older US adults following incident VTE was 3.1% (95% CI 3.0-3.2) at 30 days and 19.6% (95% CI 19.2-20.1) at 1 year. For cancer-related VTE events, the age-sex-race-standardized risk was 6.0% at 30 days and 34.7% at 1 year. The standardized 30-day and 1-year risks were higher among non-White beneficiaries and among those with low SES. One-year mortality risk decreased 0.28 percentage points per year (95% CI 0.16-0.40) on average across the study period, with no trend observed for 30-day mortality risk. In sum, all-cause mortality risk following incident VTE has decreased slightly in the last decade, but racial and socio-economic disparities persist. Understanding patterns of mortality among demographic subgroups and in cancer-associated events is important for targeting efforts to improve VTE management.

Thrombogenesis-associated genetic determinants as predictors of thromboembolism and prognosis in cervical cancer

Venous thromboembolism (VTE) is a leading cause of death among cancer patients. Khorana score (KS) is the most studied tool to predict cancer-related VTE, however, it exerts poor sensitivity. Several single-nucleotide polymorphisms (SNPs) have been associated with VTE risk in the general population, but whether they are predictors of cancer-related VTE is a matter of discussion. Compared to other solid tumours, little is known about VTE in the setting of cervical cancer (CC) and whether thrombogenesis-related polymorphisms could be valuable biomarkers in patients with this neoplasia. This study aims to analyse the effect of VTE occurrence on the prognosis of CC patients, explore the predictive capability of KS and the impact of thrombogenesis-related polymorphisms on CC-related VTE incidence and patients’ prognosis regardless of VTE. A profile of eight SNPs was evaluated. A retrospective hospital-based cohort study was conducted with 400 CC patients under chemoradiotherapy. SNP genotyping was carried on by using TaqMan® Allelic Discrimination methodology. Time to VTE occurrence and overall survival were the two measures of clinical outcome evaluated. The results indicated that VTE occurrence (8.5%) had a significant impact on the patient’s survival (log-rank test, P < 0.001). KS showed poor performance (KS ≥ 3, χ2, P = 0.191). PROCR rs10747514 and RGS7 rs2502448 were significantly associated with the risk of CC-related VTE development (P = 0.021 and P = 0.006, respectively) and represented valuable prognostic biomarkers regardless of VTE (P = 0.004 and P = 0.010, respectively). Thus, thrombogenesis-related genetic polymorphisms may constitute valuable biomarkers among CC patients allowing a more personalized clinical intervention.

Abstract P623: Long-Term Mortality and Causes of Death After Venous Thromboembolism: The Atherosclerosis Risk in Communities Study

Background: Each year in the U.S, 60,000-100,000 people die of venous thromboembolism (VTE), but little is known about mortality and causes of death over the long-term after VTE. Hypotheses: VTE, especially cancer-related VTE, is associated with poor long-term survival. Cancer and circulatory diseases are the main causes of death after VTE. Methods: Atherosclerosis Risk in Communities (ARIC) cohort participants, free of VTE at baseline (n=15,516), were followed (1986-2019) to identify first-time VTE (classified as unprovoked, cancer-provoked, or other-provoked, e.g., after surgery) and deaths. ICD10 codes were used to define cause of death. The proportion who died for each cause of death after first VTE, by type of VTE, was tabulated. Hazard ratios (HRs) of death by type of VTE were estimated with Cox proportional hazards models adjusted for age, race, gender, and pre-baseline cancer. Survival rates were visualized by adjusted survival curves. Results: Over a maximum follow-up of 33 years, 1,076 participants had first-time VTE; 441 were unprovoked, 271 were cancer-provoked, 364 were other-provoked. Mean age at first VTE was 74. After unprovoked VTE, 37% died of circulatory diseases (excluding VTE) and 13% of cancer. Those values were 35% and 13% for other-provoked VTE. By contrast, for cancer-provoked VTE, 80% died of cancer and 10% of circulatory diseases (excluding VTE). In the Figure , those with VTE had poorer long-term survival than 14,400 participants without VTE, and cancer-provoked VTE had the highest mortality. Overall, the HR of death was 2.75 (95% CI: 2.49-3.05) for those with vs without VTE. Those with cancer-provoked VTE had the highest HR, 10.02 (95% CI 8.81-11.40), but those with unprovoked and other-provoked VTE also had higher mortality than those without VTE. Conclusions: In this study, long-term survival after VTE was poor. Apart from cancer-provoked VTE, circulatory diseases were the primary causes of death after VTE. Optimizing cardiovascular prevention could improve long-term survival of patients with VTE.

Risk factors of venous thromboembolism associated with Oral maxillofacial-head and neck cancer

The association between venous thromboembolism (VTE) and malignancy has been demonstrated by a large number of studies, cancer is associated with thrombosis, which also has an impact on the proliferation and extension of cancer. The pathogenesis of cancer-related venous thromboembolism is complex, and the formation of thrombosis is the result of the complex interaction of multiple factors. This article reviews the pathological mechanism and related factors of venous thromboembolism associated with oral maxillofacial-head and neck malignancies as follows, by discussing the risk factors of VTE in patients with o oral maxillofacial-head and neck malignancies, more clearly understands the pathogenesis and risk factors of VTE associated with it, better prevent VTE in clinical practical application, strengthen risk assessment, improve the understanding of VTE related factors, do a good job in the education of patients and medical staff, individualized management and anticoagulant therapy for patients, close follow-up and regular review after treatment, so as to improve the life treatment of patients, prolong the survival time, and reduce the occurrence of VTE associated with oral maxillofacial head and neck malignancies.

Prevalence and incidence of deep venous thrombosis and pulmonary embolism in 2 regions in Turkey (A sub-analysis of CAT-TR study)

Aim: Venous thromboembolism (VTE) is a relatively common public health problem. In addition to increasing mortality due to complications, it also causes an increase in the cost of the country's economy and loss of labor due to the morbidity it creates. Considering that the recurrence of VTE is a common condition, the importance of this disease for the society increases even more. Although we have come a long way in treatment and follow-up, we see that VTE and its related complications maintain their place as a significant risk factor in the society at increasing rates. Material and Methods: This is an additional analysis of a multicentral, retrospective descriptive study, CAT-TR (Assessment of Patient Characteristic in Cancer Associated Venous Thrombosis in Turkey). The aim of the CAT-TR study was to evaluate patient characteristic and treatment patterns of cancer-induced VTE in Turkey. This article aims to evaluate the incidence and prevalence of cancer-induced VTE in two regions of Turkey between January 01, 2016 and December 31, 2019. Results: In our study, the 4-year prevalence of Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) in Central Anatolia and Marmara was 86.43, 103.56 and 105.68, 98.04 per 100.000 people, respectively. The cumulative incidence of cancer-related VTE in the Central Anatolian and Marmara populations is 17.22 and 6.71 per 100.000 people, respectively. Conclusion: The values we found in the prevalence and incidence study of VTE will be very valuable in terms of being a reference for us in the treatment and prevention of the disease. We believe that this study will shed light on new studies for diseases that may cause VTE in larger populations and strategies to be followed in prevention.

Bleeding risk in patients with multiple myeloma treated for venous thromboembolism: a MarketScan analysis

BackgroundMultiple myeloma (MM) is associated with high risk of venous thromboembolism (VTE). Thromboprophylaxis is thoroughly studied in MM. Contrarily, studies assessing the risk of bleeding in people with MM on anticoagulation are lacking. ObjectivesTo determine the rate of serious bleeding in patients with MM receiving anticoagulation for VTE and the clinical factors associated with bleeding risk. MethodsUsing the MarketScan commercial database, we identified 1298 people with MM treated with anticoagulation for incident VTE events between 2011 and 2019. Hospitalized bleeding was identified using the Cunningham algorithm. Rates of bleeding were calculated and Cox regression identified risk factors for bleeding. ResultsBleeding occurred in 51 (3.9%) cases during median follow-up of 1.13 years. Rate of bleeding among patients with MM on anticoagulation was 24.0 per 1000 person-years. In adjusted regression, factors associated with increased bleeding included age (HR, 1.31 per 10-year increase; 95% CI, 1.03-1.65), Charlson comorbidity index (HR, 1.29 per SD increase; 95% CI, 1.02-1.58), use of antiplatelet agents (HR, 2.4; 95% CI, 1.03-5.68), diabetes (HR, 1.85; 95% CI, 1.06-3.26), and renal disease (HR, 1.80; 95% CI, 1.05-3.16). Cumulative incidence of bleeding was 4.7%, 3.2%, and 3.4% for warfarin, low molecular weight heparin, and direct oral anticoagulants, respectively. ConclusionIn this real-world analysis, the rate of bleeding in people with MM on anticoagulation was comparable to those in other subsets of cancer-related VTE. Bleeding rate was lower with low molecular weight heparin and direct oral anticoagulants than warfarin. Higher comorbidity index, diabetes, antiplatelet agent use, and renal disease were risk factors for serious bleeding.

Early Time Courses of Recurrent Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer

Introduction The CARAVAGGIO trial was a multinational, randomised, investigator initiated, open-label with blind outcome assessment, noninferiority trial which demonstrated noninferiority of apixaban to dalteparin for treatment of cancer related venous thromboembolism (VTE) without an increased risk of major bleeding. In patients with acute VTE, the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation (1). We sought to evaluate the efficacy and safety of apixaban during the initial high-risk phase of treatment in patients with cancer associated VTE. Specifically, we performed a pre-specified sub-analysis of the time courses of recurrence and bleeding, with the aim to determine the incidence after 7, 30 and 90 days of treatment with apixaban compared with dalteparin. Methods The study design and methods of the CARAVAGGIO trial (CARAVAGGIO; NCT03045406; https://clinicaltrials.gov/ct2/show/NCT03045406) have been described (2). Briefly, CARAVAGGIO compared the efficacy and safety of apixaban with dalteparin in consenting patients who had active cancer and a newly diagnosed symptomatic or incidental proximal lower-limb deep-vein thrombosis (DVT) or pulmonary embolism (PE). Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed VTE. The primary safety outcome was major and clinically relevant non-major (CRNM) bleeding. Results The CARAVAGGIO study enrolled 1170 patients from 119 centres in eleven countries from April 2017 through June 2019); 1155 patients were included in the modified intention-to-treat analysis. The demographic and clinical characteristics of the patients were similar in the two treatment groups. Of the 78 recurrent VTE events 11 (14.1%) occurred in the first 7 days, 35 (44.8%) in the first 30 days and 63 (80.7%) in the first 90 days. Recurrent events occurred in 6 (1.0%) in the apixaban group and 5 (0.9%) in the dalteparin group (RR 1.21; 95% CI 0.37-3.93) by day 7, 15 (2.6%) in the apixaban group and 20 (3.5%) in the dalteparin group (RR 0.75; 95% CI 0.39-1.46) by day 30, and in 27 (4.7%) in the apixaban group and 36 (6.2%) in the dalteparin group (RR 0.75; 95% CI 0.46-1.23) by day 90. By 6 months, recurrent events occurred in 32 (5.6%) in the apixaban group and 46 (7.9%) in the dalteparin group (RR 0.70; 95% CI 0.45-1.08). (Table 1). During the six months of treatment, major and CRNM bleeding occurred in 70 patients who received apixaban (12.2%) and in 56 patients who received dalteparin (9.7%) (RR 1.26; 95% CI 0.90-1.75). Of the total 126 bleeding events, 24 (19.0%) occurred during the first 7 days; 58 (46.0%) during the first 30 days, and 89 (70.6%) during the first 90 days. Bleeding events occurred in 14 (2.4%) in the apixaban group and 10 (1.7%) in the dalteparin group (RR 1.40; 95% CI 0.63-3.14) by day 7, 30 (5.2%) in the apixaban group and 28 (4.8%) in the dalteparin group (RR 1.08; 95% CI 0.65-1.78) by day 30, and in 46 (8.0%) in the apixaban group and 43 (7.4%) in the dalteparin group (RR 1.07; 95% CI 0.72-1.60) by day 90. The Kaplan-Meier plot of time to recurrent VTE and major and CRNM bleeding is shown in figure 1. Conclusion The results of this sub-analysis of the CARAVAGGIO trial demonstrate no difference of oral apixaban to subcutaneous dalteparin at all time points. Specifically, there was no increase in recurrent VTE or bleeding events at 7 days, 30 days, 90 days and 6 months. This supports early initiation of oral anticoagulation. Oral versus subcutaneous anticoagulation has the advantage of ease of administration and outpatient delivery which may improve patients’ quality of life - an important consideration in patients with cancer. Reference 1. Raskob GE, Gallus AS, Sanders P, Thompson JR, Agnelli G, Buller HR, et al. Early time courses of recurrent thromboembolism and bleeding during apixaban or enoxaparin/warfarin therapy. A sub-analysis of the AMPLIFY trial. Thrombosis and haemostasis. 2016;115(4):809-16. 2. Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. New England Journal of Medicine. 2020;382(17):1599-607. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence and Predictors of Recurrence and Mortality Following First Venous Thromboembolism Among the Saudi Population: Single-Center Cohort Study.

BackgroundLittle is written about recurrence and mortality rates after a first episode of venous thromboembolism (VTE) among Saudi population.AimDetermine incidence rates and assess predictors of recurrence and mortality following the first VTE event.Patients and MethodsA total of 1124 patients aged ≥18 years with symptomatic VTE confirmed by imaging tests were evaluated. The incidence of VTE recurrence and mortality were assessed. The association between patient characteristics, and VTE recurrence and mortality was explored by estimating the hazard ratio (HR) and 95% confidence interval (CI). The difference between cancer-related, provoked and unprovoked VTE in terms of recurrence and mortality was explored using Kaplan–Meier curves.ResultsThe annual incidence rate of the first VTE was 1.7 per 1000 patients. Of 1124 patients with first VTE, 214 (19%) developed recurrent VTE, and 192 (17%) died with overall incidence rates of 15.8 per 100 person-years (95% CI, 13.8–18.0) and 10.0 per 100 person-years (95% CI, 8.7–11.5). Intensive care unit (ICU) admission (HR, 2.15; 95% CI, 1.67–3.10), presence of active cancer (HR, 2.97; 95% CI, 1.87–3.95), immobilization (HR, 2.52; 95% CI, 1.79–3.67), infection (HR, 2.32; 95% CI, 1.94–3.45), and pulmonary embolism ± deep venous thrombosis (HR, 2.22; 95% CI, 1.56–3.16) were found to be independent predictors of recurrent VTE. Recurrence carries a high hazard of mortality (HR, 5.21; 95% CI, 3.61–7.51). The estimated median time to VTE recurrence was lower in cancer-related VTE (18.7 months) compared with provoked (29.0 months) and unprovoked VTE (28.4 months). The estimated survival median time was lower in cancer-related VTE (21.8 months) compared with provoked (30.5 months) and unprovoked VTE (29.8 months).ConclusionImmobilization and presence of active cancer, infection, and PE ± DVT were significant predictors of recurrent VTE. Patients who developed recurrent VTE had a 5.2-fold higher hazard of mortality compared with patients with no VTE recurrence.

The Diagnostic Value of the Systemic Immune-Inflammation Index for Venous Thromboembolism in Lung Cancer Patients: A Retrospective Study

Background Venous thromboembolism (VTE) is considered a common complication in lung cancer patients. Despite its widespread use, the Khorana score performed moderately in predicting VTE risk. This study aimed to determine the diagnostic utility of the Systemic Immunoinflammatory Index (SII) and to create a novel nomogram for predicting VTE in patients with pulmonary carcinoma. Materials and Methods The data, like clinical features and laboratory indicators, of inpatients diagnosed with lung cancer from March 2019 to March 2020 were collected and analyzed. Univariate and multivariate logistic analyses were performed to confirm the risk factors and then construct a nomogram model. The calibration curve and clinical decision curve analysis (DCA) were used to assess the model's fitting performance. The receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the diagnostic value of SII and the nomogram. Results This study enrolled 369 lung patients with a VTE morbidity rate of 23.33%. The patients with VTE had higher SII levels than the non-VTE group (1441.47 ± 146.28 vs. 626.76 ± 26.04, P < 0.001). SII is the stronger correlator for VTE among inflammatory markers, of which the optimal cut-off value was 851.51. Univariate and multivariate analysis revealed that the age, metastasis, antitumor treatment, hemoglobin<100 g/L, SII>851.51 × 109/L, and D-dimer>2 folds were independent risk factors for lung cancer-related VTE, and a new prediction nomogram model was constructed based on them. ROC curve analysis showed the AUC of the new model and Khorana score were 0.708 (0.643-0.772) and 0.600 (0.531-0.699). Conclusion The SII was a simple and valuable biomarker for VTE, and the new nomogram model based on it can accurately forecast the occurrence of VTE. They can be utilized in clinical practice to identify those at high risk of VTE in lung cancer patients.

Guideline for the prevention and management of perioperative venous thromboembolism in thoracic malignancies in China (2022 version)

Improving the standardized prevention rate of venous thromboembolism (VTE) is one of the national health care quality and safety improvement goals for 2022. The incidence of cancer-related VTE is significantly higher than that of non-cancer-related VTE, and there is currently a gap in domestic guidelines for perioperative VTE prevention in thoracic malignancies. China Embolism-thrombosis after Surgery of Thorax (ChEST) Study Group has taken the lead in formulating the guideline which adopts the Grading of Recommendation Assessment, Development Evaluation approach for evidence-based assessment and a content-oriented chapter structure. It is hoped by ChEST Study Group that the promulgation of this guideline will help improve the comprehensive knowledge of prevention and management of perioperative VTE in thoracic malignancies and further standardize the diagnosis and treatment of VTE among thoracic surgeons.

Predicting major bleeding events in anticoagulated cancer patients with venous thromboembolism using real-world data and machine learning.

e18744 Background: Evidence regarding the clinical predictors of bleeding risk in patients with cancer and venous thromboembolism (VTE) is lacking. Our aim was to develop a predictive model to assess the risk of major bleeding (MB) in anticoagulant-treated patients with active cancer during the first 6 months following VTE diagnosis. Methods: Observational, retrospective, and multicenter study based on the secondary analysis of unstructured clinical data in electronic health records (EHRs). Using the EHRead technology, based on Natural Language Processing (NLP) and machine learning (ML), data were collected from EHRs from 9 Spanish hospitals between 2014 and 2018. The study population comprised all adult cancer patients with a diagnosis of VTE under anticoagulant treatment and no history of MB. This population was downsampled to prevent bias and class imbalance. A total of 94 patient characteristics were explored, and Random Forest (RF) feature selection was performed to identify the most relevant predictors. Multiple algorithms were used to train different prediction models, which were subsequently validated in a hold-out dataset. The model with the best performance metrics (i.e., ROC-AUC) was selected as the final model. Results: Among a source population of 2,893,208 patients, 21,227 anticoagulant-treated patients with VTE and active cancer were identified from EHRs. Of these, 53.9% men, with a median age (Q1, Q3) of 70 (59,80) years. The median duration of follow up across all patients was 0.7 (0.11, 2.03) years. During the study period, estimated in-hospital prevalence of cancer-related VTE was 5.8 %. The most common type of VTE at baseline was deep vein thrombosis (68.2 % of patients), followed by pulmonary embolism (28.4%). The most frequent primary cancers were colorectal (10.1%) and lung cancer (8.5 %). Of all trained and validated models, the RF approach yielded the best performance, with a ROC-AUC = 0.7. The following predictors of MB were identified: hemoglobin levels, presence of metastasis, patient’s age, platelet count, leukocyte count, and serum creatinine levels. Conclusions: This is the first multicenter study to use NLP to extract the unstructured information from EHRs to develop a predictive model for MB in anticoagulated cancer patients with VTE. These results may improve the prevention and management of bleeding in these patients.

Effectiveness and Safety of Lower Dose of Rivaroxaban for Cancer-Related Venous Thromboembolism: A Retrospective Cohort Study.

Primary and recurrent venous thromboembolism (VTE) commonly occur in patients with cancer. However, because of the National Health Insurance regulations, available dosage forms, and clinical conditions, the prescribed dose of rivaroxaban may not be consistent with its recommended dose. To evaluate the 6-month recurrence rate of VTE and safety of rivaroxaban for patients with cancer. Patients with new cancer diagnosis or recurrence from 2014 to 2018 who initiated rivaroxaban for VTE from January 2015 to January 2019 were included. We set the rivaroxaban initiation date as the index date and followed up the patients for 180 days. We collected information regarding the starting and maintenance dose/frequency and the treatment duration. The efficacy outcome was the recurrence of VTE within 180 days. The safety outcome included the major bleeding rate and clinically relevant nonmajor bleeding (CRNMB) rate. Approximately, 46.2% of the 65 included patients received a standard starting dose, and 45% of patients received a maintenance dose above 15 mg (median: 23.9 and 13.1 mg per day, respectively). Two-thirds of the patients stopped treatment within 180 days. Recurrent VTE occurred in 2 (3.1%) patients within 6 months. The major bleeding rate was 7.7%, and the CRNMB rate was 3.1%. The 6-month recurrence rate of VTE and safety profile were similar between the lower and standard dose of rivaroxaban. This result may be applied to the institutions with dosage availability limited by formulary regulation and patients who cannot use full dose because of clinical considerations.

Microparticles and D-dimers improve prediction of chemotherapy-associated thrombosis in cancer patients

Background: The cancer is associated with a state of hypercoagulability, which may be the cause of venous thromboembolism (VTE), representing an undeniable cause of morbidity and mortality. Our study aimed to investigate the role of hypercoagulability markers (D-dimers, microparticles, and V Leiden mutation) in predicting cancer-associated VTE. Methods: A prospective cohort study was conducted among cancer patients who will receive chemotherapy in the Medical Oncology and Hematology departments of the EHU of Oran, Algeria from February 2013 to May 2015, followed by an observation period of two years. First, we evaluated the risk of cancer-related VTE by hypercoagulability parameters (D-dimers, microparticles, V Leiden mutation). In the second step, we tested the predictive value of the Khorana risk score (KRS) of cancer-related VTE. Then, we developed and tested the predictive value of an expanded score based on the addition of predictive biomarkers to the KRS parameters. Results: A total of 165 patients were included in our study whose median age was 62 years. More than half were males (52.7%). After an observation period of 2 years, ten patients (6.0%) developed a VTE. Among the criteria studied, only the D-dimers and the microparticles were predictive of VTE in cancer. The positive predictive value (PPV) of the KRS was 13.6%, and the negative predictive value (NPV) was 97.9%. After adding two predictive biomarkers (D-dimers and microparticles), the expanded score had a better predictive value with a PPV of 23.5% and a VPN of 98.6%. Conclusion: The addition of hypercoagulability biomarkers (microparticles and D-dimers) to the routine clinical and biological parameters of the KRS enhances the predictive potential of VTE risk in cancer.

Abstract P134: Venous Thromboembolism Mortality And Trends In U.S. Adults 65+: 2011-2018

Introduction: Venous thromboembolism (VTE) afflicts approximately 1 million Americans annually. Over the past decade there has been a movement towards outpatient management of uncomplicated acute events and use of oral anticoagulant agents for treatment. The purpose of this study was to update the estimated rates and trends of VTE-related mortality in older adults in the U.S. Methods: Medicare 20% sample claims data from 2011 to 2018 were used to create a cohort of beneficiaries with a VTE event using validated ICD codes. All-cause mortality, identified by National Death Index linkage, was assessed at 30 days and 1 year after VTE for each year over the full study period. Subgroup analyses were conducted by age, sex, race, and cancer-related VTE. Estimates were standardized for age, sex, and/or race, where appropriate. Results: The study included 113,826 VTE patients, mean age 77 years (SD=8), and were 61% (n=69,338) female. The cohort was 84% (n=95,976) non-Hispanic White, 11% (n=12,051) non-Hispanic Black, and 5% (n=5,799) other/unknown, and 34% (n=38,252) VTE events were cancer-related. Overall, 30-day and 1-year mortality was 2.5% (2,857 of 113,141) and 19.6% (19,621 of 100,035) (Table). Mortality rates increased with age and were slightly higher in men and in non-White patients. Cancer-related VTE was associated with greater 30-day (4.7% vs. 1.5%) and 1-year mortality (32.9% vs. 12.9%) than non-cancer VTE. Mortality rates remained steady over the study period in most subgroups. Mortality following cancer-related VTE appeared to decrease steadily over time for both 30-day (from 5.4% in 2011 to 4.4% in 2018) and 1-year mortality (from 36.3% in 2011 to 31.6% in 2017). Conclusions: Among contemporary VTE patients aged 65 and older, the risk of mortality is 2.5% at 30 days and 19.6% at 1 year. Despite notable changes to VTE management, all-cause mortality in Medicare beneficiaries with VTE was largely unchanged from 2011 to 2018, except for decreasing mortality following cancer-related VTE.

Efficacy and safety of direct oral anticoagulants versus warfarin in elderly patients with cancer-associated venous thromboembolism

Background Little is known about the effects of direct oral anticoagulants (DOACs) in cancer[1]related venous thromboembolism patients. Methods Data of patients with cancer-related venous thromboembolism (VTE) were retrieved from King Abdulaziz Medical City Database during 2016–2020. We excluded patients who were not using oral anticoagulants, used anticoagulants for &lt;30 days, used 2 agents concomitantly or switched anticoagulants,were aged &lt;65. The primary outcomes were recurrent VTE,major bleeding, and death from any cause. Results We identified 717 patients who received a diagnosis of cancer-related VTE. After the exclusion criteria were applied, 445 patients remained, 298 were used warfarin, and 147 were received NOACs. Both groups were followed up for 12±2 months. The mean age of the patients was 71 ± 8 in the DOACs group and 76 ±6 in the warfarin group (p &gt; 0.05); 48.24% of patients in the DOAC group and 46.98% of patients in the warfaringroup were men (p &gt; 0.05). The mean HAS-BLED score was 3.7 ± 3.8 in the NOAC group and 3.8 ± 3.9 in the warfaringroup (p &gt; 0.05). Furthermore, among patients with cancer-related VTE, DOAC was associated with no difference in major bleeding or recurrence events (CRR = 0.91, 95% CI = 0.78–1.05; CRR = 0.63, 95% CI = 0.52–0.77, respectively), and significantly reduced death from any cause (aHR = 0.65, 95% CI = 0.52–0.80) compared with warfarin. Conclusions In elderly patients with cancer-related VTE, DOAC was associated with reduced death from any cause compared with warfarin, whereas no difference in major bleeding or recurrent VTE were observed between these treatment modalities.

Thrombin Generation to Predict the Risk of Venous Thromboembolism Recurrence, Major Bleeding and Death in the Elderly: A Prospective Multicenter Cohort Study

Introduction: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), constitutes a worldwide major health issue, and a leading cause of death. VTE incidence increases exponentially with age mainly due to the accumulation of risk factors and comorbidities predisposing to thrombosis. This leads to greater morbidity impact of VTE on elderly patients, who are also at higher risk of bleeding. Consequently, identification of older patients who might benefit from indefinite anticoagulation treatment is paramount. In order to facilitate the identification of these patients, the benefit/risk ratio should be carefully evaluated by considering clinical and laboratory information. Thrombin activity can be recorded by continuously measuring cleavage of a fluorescent substrate, resulting in a thrombin generation (TG) curve. Recent association studies show promising data of thrombin generation parameters predicting first VTE in elderly (Wang H et. al. RPTH 2021, 5:e12536). However, the predictive ability of thrombin generation for recurrent VTE, major bleeding and mortality in the elderly is unknown. The goal of this study was to prospectively investigate the performance of the TG assay one year after index VTE in predicting the risk of VTE, recurrence, major bleeding and mortality up to 2 years in elderly population.Methods: The study was conducted as part of the Swiss Cohort of Elderly Patients with VTE (SWITCO65+), a prospective multicenter cohort study to assess medical outcomes and quality of life in elderly patients with acute VTE in Switzerland. For the present study, the clinical outcomes were VTE recurrence, major bleeding and mortality, which were assessed parallel to clinical data of thrombosis and other general laboratory parameters including thrombophilia testing in over a 3-year period. Blood samples for assessment of TG parameters were drawn 12 month after the index VTE. Venous blood was drawn after minimal venostasis and processed by double centrifugation according to the recommendation of the subcommittee of the Scientific and Standardization Committee of ISTH. TG measurements were performed with the calibrated automated thrombogramm assay (Stago, Asnières-sur-Seine, France) in two experimental settings: 1pM tissue factor (TF) with/without thrombomodulin (TM) and 13.6 pM TF with/without activated protein C (APC). In addition, reference plasma (Cryocheck Reference Control Normal, PrecisionBiologic, Dartmouth, Canada) was tested in all experiments in order to correct day-to-day variations. Lag time, velocity index, time to peak, peak height, endogenous thrombin potential (ETP) were measured and peak and ETP ratio obtained in presence/absence of TM or APC were calculated. Results from the reference plasma were used to calculate the normalized ETP and peak ratio in 1 pM setting and peak ratio in 13.6 pM TF setting.Results: TG was assessed in 565 patients 12 months after the index VTE. At this time, 59% of patients were still anticoagulated. Eleven percent of them had cancer-related VTE, 20% provoked VTE and 68% unprovoked VTE. The prevalence of inherited risk factors for VTE was in line with previous reports on European patients with VTE.Patients still anticoagulated 12 months after the index VTE were less likely to develop recurrent VTE in the next 24 months than patients without anticoagulation. However, the incidence of major bleeding and mortality was comparable in anticoagulated and non-anticoagulated patients.TG was faster and lower in anticoagulated than in non-anticoagulated patients.Some thrombin generation parameters measured 12 months after the index VTE (Figure 1) were discriminatory for VTE recurrence, major bleeding and mortality (Table 1). In addition, several thrombin generation parameters measured in patients not under anticoagulation 12 months after the index VTE were associated with an increased risk of VTE recurrence, major bleeding and mortality up to 24 months. These associations remained after adjustment for potential confounding factors for the risk of VTE recurrence, major bleeding and mortality (Table 2).Conclusion: In elderly patients, several parameters of thrombin generation were associated with VTE recurrence, major bleeding and/or mortality. These findings may serve as the basis for validation in a prospective interventional outcome trial. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Arguments for Using Direct Oral Anticoagulants in Cancer-Related Venous Thromboembolism.

(1) Background: Patients with cancer with a hypercoagulable state present an increased incidence of venous thromboembolism (VTE). Neoplastic patients with concurrent VTE undergoing anticoagulant treatment face a series of issues. (2) The aim of the present paper is to systematically summarize current VTE management in patients with neoplasia and to review the current clinical evidence from meta-analyses of randomized controlled trials and guidelines regarding the administration of direct oral anticoagulants (DOACs) for cancer-associated VTE. (3) Search Strategy: We performed a review on meta-analyses of randomized controlled trials and guidelines in favor of the administration of DOACs in patients with cancer-associated VTE published in the last 6 years in the Medline (PubMed) and Embase databases. (4) Results: 21 meta-analyses, 14 randomized controlled studies comparing DOACs to VKAs and LMWH, and 7 national and international guidelines were identified. We identified five studies that show the antineoplastic effect of DOAC on experimental models. (5) Conclusions: DOACs can be seen as the first choice for VTE treatment in neoplastic patients who have a low risk of bleeding, who do not have severe renal impairment, and who are not undergoing treatments that could interact with DOAC’s mechanism of action.