Cancer-associated Venous Thrombosis Research Articles

Effectiveness and safety of continuous low-molecular-weight heparin versus switching to direct oral anticoagulants in cancer-associated venous thrombosis

Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35–0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61–0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83–1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.

Cancer complicated by thrombosis and thrombocytopenia: still a therapeutic dilemma

Individuals who have thrombocytopenia and cancer-associated thrombosis (CAT) are difficult to manage because they have a high risk of bleeding and recurrent thrombosis. The International Society on Thrombosis and Haemostasis guidelines for the management of thrombocytopenia in patients with CAT suggest two main approaches: either complete anticoagulation with transfusion support if necessary, or dose-modified anticoagulation while the platelet count is <50×109/L. Nevertheless, rather than being based on information from randomized controlled trials (RCTs), these recommendations were based on expert consensus. Recent research from two different countries has shown how this cohort’s management and results vary widely. While the United Kingdom study, Cancer-Associated Venous Thrombosis and Thrombocytopenia, found no significant differences in bleeding or recurrent thrombosis between full dose and modified dose groups, the North American Thrombocytopenia Related Outcomes with Venous thromboembolism study demonstrated a significantly lower risk of bleeding events in those receiving modified dose anticoagulation compared to full dose, without an increased risk of recurrent VTE. Therefore, an RCT is required to assess the best course of action for patients with CAT and thrombocytopenia. To define the standard of care for the management of patients with CAT and thrombocytopenia, a full-scale trial called the START randomized trial (STrategies for Anticoagulation in patients with thRombocytopenia and cancer-associated Thrombosis) is an international, multi-site pilot study that compares the use of platelet transfusions plus higher dose anticoagulation to modified dose anticoagulation in patients with thrombocytopenia and CAT receiving anticoagulation.

Cancer-associated venous thrombosis in adults (second edition): A British Society for Haematology Guideline.

A shared decision on the most appropriate agent for the treatment of cancer-associated thrombosis should consider the following factors, which should be reassessed as patients continue along their cancer care pathway: risk of bleeding; tumour site; suitability of oral medications; potential for drug-drug interactions; and patient preference and values regarding choice of drug. Continuing anticoagulation beyond 6 months in patients with cancer-associated venous thromboembolism and active cancer is recommended.

Haemostatic gene variations in cervical cancer-associated venous thrombosis: considerations for clinical strategies.

Venous thromboembolism (VTE) is a life-threatening haemostatic disease frequently diagnosed among the cancer population. The Khorana Score is currently the primal risk assessment model to stratify oncological patients according to their susceptibility to VTE, however, it displays a limited performance. Meanwhile, intensive research on VTE pathophysiology in the general population has uncovered a range of single-nucleotide polymorphisms (SNPs) associated with the condition. Nonetheless, their predictive ability concerning cancer-associated thrombosis (CAT) is controversial. Cervical cancer (CC) patients undergoing chemoradiotherapy often experience VTE, which negatively affects their survival. Thus, aiming for an improvement in thromboprophylaxis, new thrombotic biomarkers, including SNPs, are currently under investigation. In this study, the predictive capability of haemostatic gene SNPs on CC-related VTE and their prognostic value regardless of VTE were explored. Six SNPs in haemostatic genes were evaluated. A total of 401 CC patients undergoing chemoradiotherapy were enrolled in a retrospective cohort study. The implications for the time to VTE occurrence and overall survival (OS) were assessed. CAT considerably impacted the CC patients' OS (log-rank test, P < 0.001). SERPINE1 rs2070682 (T > C) showed a significant association with the risk of CC-related VTE (CC/CT vs. TT, log-rank test, P = 0.002; C allele, Cox model, hazard ratio (HR) = 6.99 and P = 0.009), while F2 rs1799963 (G > A) demonstrated an important prognostic value regardless of VTE (AA/AG vs. GG, log-rank test, P = 0.020; A allele, Cox model, HR = 2.76 and P = 0.026). For the remaining SNPs, no significant associations were detected. The polymorphisms SERPINE1 rs2070682 and F2 rs1799963 could be valuable tools in clinical decision-making, aiding in thromboprophylaxis and CC management, respectively.

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.

Primary prevention of cancer-associated venous thrombosis: Rationale and challenges in clinical practice

Cancer-associated venous thrombosis (CAT) is a common, multifactor event known to complicate the course of cancer and jeopardize a patient's prognosis. The current guidelines regarding the prevention of CAT are sometimes considered insufficiently precise about specific situations, or are poorly applied. The expected benefits of thromboprophylaxis are balanced by the risk of major bleeding induced by anticoagulation, which implies a need to accurately identify ambulatory patients at high risk of thrombosis or hemorrhage. The Khorana score is commonly used for this, but is limited by the non-reproducibility of predicted performance across cancer types, and by the fact that antitumor treatment and cardiovascular risks are not included. The COMPASS-CAT score, which includes those two aspects, was found to be a more accurate predictor of venous thromboembolism in patients with lung cancer, and to better distinguish between patients at low or high risk of thrombosis. The frailty of patients with cancer is also a major issue, and should be taken into account when thromboprophylaxis is considered. According to current guidelines, CAT prophylaxis should be considered for hospitalized patients, those for whom surgery is scheduled, or those with pancreatic cancers. In ambulatory patients, decisions should be made according to patient, cancer and antitumoral treatment characteristics. Low molecular weight heparin is the gold standard of CAT prophylaxis. Despite increased risks of bleeding or drug-drug interactions in cancer patients, direct oral anticoagulants could be alternate options for high-risk ambulatory patients that should be accompanied by a careful global analysis of benefits, harms, and patient preferences.

Mechanisms of platelet activation in cancer-associated thrombosis: a focus on myeloproliferative neoplasms.

Platelets are anucleate blood cells that play key roles in thrombosis and hemostasis. Platelets are also effector cells in malignancy and are known to home into the microenvironment of cancers. As such, these cells provide central links between the hemostatic system, inflammation and cancer progression. Activation of platelets by cancers has been postulated to contribute to metastasis and progression of local tumor invasion. Similarly, cancer-activated platelets can increase the risk of development of both arterial and venous thrombosis; a major contributor to cancer-associated morbidity. Platelet granules secretion within the tumor environment or the plasma provide a rich source of potential biomarkers for prediction of thrombotic risk or tumor progression. In the case of myeloproliferative neoplasms (MPNs), which are characterized by clonal expansion of myeloid precursors and abnormal function and number of erythrocytes, leukocytes and platelets, patients suffer from thrombotic and hemorrhagic complications. The mechanisms driving this are likely multifactorial but remain poorly understood. Several mouse models developed to recapitulate MPN phenotype with one of the driving mutations, in JAK2 (JAK2V617F) or in calreticulin (CALR) or myeloproliferative leukemia virus oncogene receptor (MPL), have been studied for their thrombotic phenotype. Variability and discrepancies were identified within different disease models of MPN, emphasizing the complexity of increased risk of clotting and bleeding in these pathologies. Here, we review recent literature on the role of platelets in cancer-associated arterial and venous thrombosis and use MPN as case study to illustrate recent advances in experimental models of thrombosis in a malignant phenotype. We address major mechanisms of tumor-platelet communication leading to thrombosis and focus on the role of altered platelets in promoting thrombosis in MPN experimental models and patients with MPN. Recent identification of platelet-derived biomarkers of MPN-associated thrombosis is also reviewed, with potential therapeutic implications.

Oncoguía de trombosis venosa asociada a cáncer: profilaxis y tratamiento 2023

People with cancer are at increased risk of developing venous thrombosis and rethrombosis (despite treatment), as well as at an increased risk of bleeding. The causes of thrombosis and bleeding vary among patients, tumor types, and cancer treatments. Cancer-associated venous thrombosis (CAVT) causes morbidity, delays in cancer treatment, impairment of quality of life and of emotional state, and increased mortality. Approximately one in ten individuals with cancer die from pulmonary thromboembolism. Reducing the risk of thrombosis in surgery, hospitalization, and in outpatients with cancer is possible with targeted, risk-based thromboprophylaxis. Treatment of CAVT should be individualized in terms of type of anticoagulant, dose, duration of treatment, and modifications of anticoagulation during invasive procedures. These guidelines present a framework for the comprehensive management of patients with cancer and venous thrombosis.

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.

Expanding the possibilities of treatment and prevention of venous thromboembolic complications in cancer patients. The role of oral anticoagulants

Improving the quality of care for patients with oncological diseases due to the improvement of methods of chemoradiotherapy and surgical interventions, accessibility and modernization of diagnostic potential, is accompanied by a steady increase in the frequency of venous thromboembolic complications, which occupy one of the leading places among the causes of death.Patients with oncological diseases are subject to various risk factors for thromboembolic complications, which are caused by the presence of a malignant neoplasm, due to the development of many coagulation abnormalities, initiating not only an increased tendency to thrombosis, but also a tendency to bleeding. Cancer-associated venous thrombosis, growing out of the framework of certain medical specialties, act as comorbid pathological conditions that require an interdisciplinary approach in developing rational methods of prevention and treatment. Improving the understanding of the pathophysiological mechanisms of venous thrombosis in cancer patients contributes to the development of modern methods of prevention and treatment, among which anticoagulant therapy plays a dominant role. The appearance of oral anticoagulants on the pharmaceutical market, the effectiveness and safety of which is confirmed by a series of randomized clinical trials, opens up new prospects for improving the quality of life and long-term survival in patients with malignant neoplasms.

Role of anticoagulants in therapy and prevention of recurrent venous thromboembolism in patients with cancer: a meta-analysis of randomized trials with apixaban

Background Venous thromboembolic complications (VTEC) are a major non-oncological cause of death of patients with malignant neoplasm (MNP). This determines the high significance of antithrombotic therapy for the treatment and secondary prevention of VTEC in this population. During recent years, low-molecular weight heparins (LMWH) have been a "gold standard" for the treatment of cancer-associated venous thrombosis (CAVT). In the recent decade, direct oral anticoagulants (DOACs) have become extensively used for the treatment and prevention of VTEC relapse in non-oncological patients and also for primary prevention of VTEC following orthopedic surgery. Taking into account the oral route of administration, the predictable and convenient pharmacokinetic profile, and the absence of need for coagulation monitoring, it seems possible to use DOACs for the treatment and secondary prevention of VTEС in oncological patients. A meta-analysis of 4 randomized clinical trials (RCTs) showed a higher efficacy of DOACs compared to LMWHs, however, with a greater risk of bleedings in CAVT. In two of four studies using apixaban (more than 40% of weight in meta-analysis), no increase in bleedings was noted.Aim The aim of this study was to perform a systematic search for comparative clinical studies with apixaban and to perform a meta-analysis to answer the question on clinical efficacy and safety of apixaban in the treatment and secondary prevention of recurrent VTEC in patients with CAVT.Material and methods The systematic search was performed in three reference databases, Medline (PubMed), Cochrane Library (CENTRAL), and eLibrary. The search was aimed at publications containing results of RCTs using apixaban for the treatment and prevention of VTEC in patients with MNP. A totality of 678 titles was found; 15 articles were selected for detailed studying, and 4 RCTs were included into the final analysis. The meta-analysis was performed according to the criteria of PRISMA guidelines. Relative risk (RR) was used as a measure of the effect. The meta-analysis was performed by the Mantel-Haenszel method using the R software. Statistical heterogeneity was evaluated with the Cochran criterion (I2); heterogeneity was considered significant at I2 ≥50 %, which was a reason for performing a random-effects meta-analysis. For this meta-analysis, the primary outcome measure was new VTECs (symptomatic or detected proximal deep vein thrombosis and/or symptomatic, detected or fatal pulmonary thromboembolism plus symptomatic upper extremity thromboses, celiac veinous thromboses, and cerebral veinous thromboses if they were included into the efficacy endpoint of the primary studies). The primary safety measure was major bleeding according to ISTH criteria. Other variables included major and clinically significant minor bleedings as well as overall death rate.Results During the systematic search, 4 RCTs were selected. The meta-analysis of the treatment and secondary prevention of VTEC in patients with MNP showed that apixaban was more effective than the active control (88% of LMWHs) in prevention of VTEC relapse. The RR was 0.59; 95 % confidence interval (CI): 0.40-0.86 in the absence of statistically significant differences from the control in the risk of major bleedings (statistically non-significant decrease by 21%), the sum of major and clinically significant minor bleedings, and overall death rate.Conclusion According to the results of the meta-analysis, the DOAC apixaban may be a drug of choice for the treatment and prevention of VTEC relapse in patients with MNO.

Anticoagulation Practice in Patients with Cancer-Associated Thrombosis: Insights from GeCAT, a German Prospective Registry Study

Introduction: Cancer-associated venous thrombosis (CAT) is a common and serious complication of active malignancies, increasing in frequency during systemic treatment and radiotherapy. Due to a high risk of recurrence and bleeding, the administration of anticoagulants for initial treatment and secondary prevention of CAT is challenging. We conducted a prospective registry study of patients with acute CAT to evaluate the way treatment is given to these patients in routine practice. Methods: From May 2015 to May 2017, all consecutive patients with acute venous thromboembolism (VTE) admitted to specialty or emergency departments of the participating hospitals in Berlin, Germany, were entered into the registry. Patients with cancer underwent extensive baseline evaluation including the type and location of thrombosis and use of anticoagulant therapy. Follow-up assessments were made at discharge and by telephone interviews at 3 and 6 months. Results: A total of 382 patients with acute CAT were enrolled in the study, representing 24.5% of all patients with thrombosis. 70.4% of CAT patients had deep vein thromboses (DVT), 48.2% had pulmonary embolism (PE), and 18.6% had concurrent PE and DVT. A significant proportion of VTE (27%) was asymptomatic and was diagnosed only incidentally. At baseline, 97.9% of the patients received anticoagulant therapy, predominantly with low-molecular-weight heparin (LMWH) (n = 334, 87.4%). Direct oral anticoagulants (DOACs) were given to 5.8% of patients, and vitamin K antagonists were rarely used (<2% of patients). Changes in the prescription of antithrombotic agents were seen at discharge from hospital and during follow-up. Overall, the use of LMWH declined during follow-up, while the proportion of patients treated with DOACs increased to 32.4% at 6 months. At baseline, the most frequently used LMWH were enoxaparin and nadroparin, but many patients were switched to once daily tinzaparin prior to discharge. Initially and after discharge, the majority of patients were treated by oncologists. Overall, 263 (68.8%) and 222 (58.1%) patients were still alive and could be contacted at 3 and 6 months of follow-up, respectively. Of these, 84.0% and 71.6% were still on anticoagulant therapy (58.6% and 36.5% on LMWH). Conclusion: In accordance with the guidelines, the majority of CAT patients received anticoagulation therapy for the recommended minimum duration of 3–6 months. LMWH remained the preferred option throughout the study, demonstrating good patient adherence. In deviation from guideline recommendations and available study results during the study period, more than a quarter of CAT patients were treated with DOACs. Only recently, DOACs have been established as another option for anticoagulation in CAT patients.

Patient Characteristics and Temporal Changes in Anticoagulation Treatment Patterns in Patients Diagnosed with Cancer-Associated Thrombosis: An Oscar-US Analysis

Background: Although guidelines include direct-acting oral anticoagulants (DOACs) as an alternative to low molecular weight heparins (LMWHs) for treatment of cancer associated venous thrombosis (CAT), specific recommendations for selection of patients for DOAC treatment vary. Recommendations for use of DOACs are driven predominantly by perceptions of risk: benefit ratio (often associated with different cancer subtypes). We sought to assess patient characteristics and temporal changes in DOAC (vs. LMWH) utilization in patients being treated in routine practice for CAT.Methods: This analysis is part of the Observational Studies in Cancer Associated Thrombosis for Rivaroxaban - United States (OSCAR-US) program. OSCAR-US is an ongoing study utilizing longitudinal patient-level medical record data from Optum for 91+ million patients seen at 700+ hospitals and 7,000+ clinics across the US. To be included in the present study, adult patients had to be diagnosed with active (primary or metastatic) cancer, undergone hospitalization, emergency department or observation unit admission associated with a primary International Classification of Diseases (ICD)-9th or -10 th revision diagnosis code for venous thromboembolism (VTE) between January 2013 and September 2020, received a DOAC or LMWH on day 7 of CAT treatment, and been active in the data set for at least 12 months prior to the CAT. Cohort assignment was based upon anticoagulant received on day 7 to increase the study's likelihood of appropriately classifying patients into their intended long-term treatment group. We defined active cancer as any cancer associated with ongoing treatment with chemotherapy, immunotherapy, radiation, or recent surgery; the presence of metastatic disease (regardless of time from initial cancer diagnosis); or provider encounter with a primary diagnosis code for cancer within the 6 months prior to the CAT. We excluded patients with an alternative indication for anticoagulation use or evidence of anticoagulation during the 12 months prior (per written prescription or patient self-report). For this analysis, year of CAT diagnosis was grouped into three mutually exclusive categories (2013-2015, 2016-2018, and 2019-2020) to represent early DOAC availability for VTE, peri-DOAC CAT trials and post-CAT guideline recommendation periods. Categorical data were reported as percentages, while continuous data were reported as means ± standard deviations (SDs). Chi-square and independent sample t-tests were used to test for differences in characteristics and treatment patterns between cohorts.Results: In total, 95,072 adult patients experiencing a VTE-related hospitalization, emergency department or observation unit visit were identified. Of these, 14,377 (15.1%) met our pre-specified criteria for active cancer; including 84.7% who received a cancer treatment modality within 6-months and/or had metastatic disease (Table). Though a majority (76.0%) of patients received parenteral therapy as their first anticoagulant upon CAT diagnosis; on day 7 of CAT management, 5325 (52.0%) were receiving a DOAC and 4925 (48.0%) a LMWH. Mean age of patients was 65.2±13.7 years, body mass index (BMI) was 29.9±7.7 kg/m2 and 55.9% were women. Pulmonary embolism (PE)±deep vein thrombosis (DVT) was present in 47.2% of patients and more frequent in patients treated with LMWH than a DOAC on day 7 (p<0.001). The most common cancer types were lung (18.3%) genitourinary (13.5%), breast (12.7%) and colorectal (10.5%) (Figure). The proportion of patients treated with a DOAC increased substantially for all cancers over the three time periods evaluated (27.5% to 55.9% to 73.2%, p<0.001). This temporal relationship of increasing DOAC use (vs. LMWH) remained consistent across individual cancer subtypes (p<0.001 for all). Mean anticoagulant treatment duration was 193±143 days for the entire cohort and was longer in patients treated with DOACs vs. LMWHs (226±138 vs. 147±138 days, p<0.001).Conclusions: In this US population, DOACs were increasingly being utilized for the management of CAT patients and for longer treatment durations than LMWHs. The finding of increasing frequency in use of DOACs vs. LMWHs appeared consistent across all major cancer subtypes. Given their common use, future analyses should evaluate the real-world effectiveness and safety of DOACs compared to LMWHs within individual cancer subtypes. [Display omitted] DisclosuresColeman: Bayer AG: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs LLC: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals: Research Funding. Abdelgawwad: Bayer AG: Current Employment. Psaroudakis: Bayer AG: Current Employment. Fatoba: Bayer AG: Current Employment. Rivera: Bayer AG: Current Employment. Brobert: Bayer AG: Current Employment.

SAFETY AND EFFECTIVENESS OF ANTICOAGULATION BASED ON AN INSTITUTIONAL RECOMMENDATION ON THE MANAGEMENT OF CANCER ASSOCIATED VENOUS THROMBOSIS

Cancer associated venous thrombosis (CAT) can affect 20% of oncologic patients. Its management is challenging due to coexistent risk of bleeding and thrombosis (VTE) recurrence, that are 6 and approximately 4 fold higher compared to non-cancer patients, respectively. Anticoagulant choice needs to be careful and can be guided by a recommendation to avoid those complications. To evaluate effectiveness and safety of anticoagulation according to a public cancer institution recommendation on CAT management. This is a retrospective cohort study carried out from October 2018 to January 2020. The recommendation on CAT management included defined criteria to select the proper anticoagulant for each patient, to make adjustments and to handle anticoagulation in challenging situations, like thrombocytopenia, in the perioperative period and facing bleeding and thrombosis recurrence. A 3-month ambulatory was scheduled to evaluate eligibility of outpatients on enoxaparin to switch to rivaroxaban (new at the institution), based on criteria defined by the recommendation. All consecutive adult oncologic outpatients on therapeutic enoxaparin in the institution were considered eligible for the ambulatory. Retrospective data on cancer, comorbidities, bleeding, VTE recurrence and death during 1 year since the first visit were captured from an electronic recording. Cumulative incidence of bleeding and VTE recurrence were calculated by Kaplan-Meier method and log-rank test. 326 patients were referred to the ambulatory and 268 were included in the analyses, with a median age of 63 years (IQR 53-71). Sixty-one percent were female and 86% had solid tumours (53% metastatic). The main sites were the gastrointestinal tract (27%), breast (12%) and lungs (10%). Forty-six percent of the patients switched to rivaroxaban and 6% were able to stop anticoagulation. From the 85 patients who remained on enoxaparin, 51.7% had some dosing adjustment (to 1.5 mg/kg/day or to prophylactic dose). The main reason for not switching to rivaroxaban was drug-drug interaction (27%). One-year cumulative incidence of VTE recurrence was 11.2% (95% CI 7.7-16.2) and of overall bleeding was 13.4% (95% CI 9.4-18.7). Major bleeding occurred in 8 out of 268 patients (2.9%). Death rate was 32%, with no one due to bleeding. No significant difference in outcomes was observed between patients who had switched or not. Severity of cancer status was considered relevant for the high rate of deaths. Cumulative incidence of bleeding as well as thrombosis recurrence were similar to the described in the literature, although many clinical trials on direct oral anticoagulants in cancer patients had a shorter period of follow-up. Recommendation-based decision on anticoagulant choice and management showed similar effectiveness and safety independently of the chosen anticoagulant. No relevant hazards due to anticoagulation were observed during the follow-up period.

Treatment of Cancer Associated Venous Thrombosis; The Cleveland Clinic Experience

Introduction:Current guidelines recommend anticoagulation with low molecular weight heparin (LMWH) over vitamin K antagonists (VKA) for the treatment of cancer associated thrombosis (CAT). The use of direct oral anticoagulants (DOACs) is gaining more popularity amongst patients and prescribers given the ease of administration and lower cost compared to LMWH. However, there is limited published data comparing LMWH vs DOACs for the treatment of CAT. Here we report patient outcomes from our clinical experience in treating CAT.Methods:We evaluated a prospective cohort of patients referred to our centralized CAT clinic at the Cleveland Clinic Taussig Cancer Institute. This clinic provides urgent outpatient consultation for adult cancer patients with clinical concern for VTE. In effort to standardize initial treatment, reduce variation in care, and minimize the need for hospitalization, a care path was created to recommend LMWH as the preferred anticoagulant for treatment of VTE with rivaroxaban as an alternative based on patient preference or cost. We evaluated clinical characteristics, anticoagulation prescription, VTE recurrence rate, and subsequent hospitalization for patients diagnosed with VTE. Continuous variables were analyzed with t-test, chi-square (or Fisher's exact) for unordered categorical data, and Cochran-Armitage test for ordered categorical data. Kruskal Wallis test for age was used when comparing all treatments and Wilcoxon rank sum test for age was used when comparing enoxaparin vs rivaroxaban.Results:Data from 608 patients seen between 8/2014 and 11/2016 were considered for analysis. Sixteen patients were excluded (15 due to missing data and one because he/she was the only patient treated with apixaban), leaving 592 patients. Males comprised 52% (308/592) of the study population, median age was 63 (range 20-95). Hematologic malignancies comprised 21% (123/586) of patients and most patients with solid tumors had metastatic disease (72%, 265/368). Within the study population, 15% (88/584) had history of prior VTE and 54% (289/537) were considered high risk based on the modified Ottawa score. (Table 1)VTE was diagnosed in 34% of patients referred to the clinic: Of these, 29% (174/529) were diagnosed with deep vein thrombosis (DVT), 2 % (12/529) with pulmonary embolism (PE), 3% (17/592) with both DVT and PE and one patient had visceral vein thrombosis. Of patients diagnosed with VTE, 25% of patients were subsequently hospitalized.Gastrointestinal, brain, and lymphoma's had a higher rate of VTE than other tumor types (45-49% vs 29-35%). Breast cancer had a lower rate of VTE than other cancer types (17%, p=0.001)Enoxaparin was the most commonly prescribed drug given to 76% (149/195) of patients. Rivaroxaban was given to 12% (23/195), 8% (16/195) were treated with Coumadin and 7 patients (4%) were not given anticoagulant therapy due to a contraindication. High Ottawa score patients received rivaroxaban less frequently than other treatments (p=0.02). Patients treated with rivaroxaban had less hospitalizations compared to patients treated with other anticoagulants (p=0.04).Of patients diagnosed with VTE, 16 (8%) had a recurrent event. There were no significant associations with sex, age, type of cancer, stage, or type of anticoagulant. Specifically, there was no difference in risk of VTE recurrence in patients treated with LMWH (11 events) vs rivaroxaban (0 events); p=0.36). The Ottawa score did not statistically correlate with recurrent VTE (0%, 6%, and 10%) for low, intermediate, and high risk, respectively (p=0.2). An increased risk of recurrent VTE was seen in patients who had personal history of VTE and in those who were hospitalized after the VTE (p=0.02 and p=0.005, respectively). Table 2Conclusion:The Cleveland Clinic provides centralized care to cancer patients diagnosed with VTE. Among patients referred to our CAT clinic, we found risk of VTE correlates with cancer type and personal history of VTE. Most of our patients received our recommended therapy, enoxaparin, but rivaroxaban was prescribed to some due to patient preference. Patients treated with rivaroxaban had fewer adverse outcomes compared to those treated with other anticoagulants. Limitations include the small sample size and greater use of rivaroxaban in lower risk patients. We found the risk of VTE recurrence was higher in those with history of VTE and in those hospitalized for their VTE event. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Management of Cancer-Associated Venous Thrombosis: A Nationwide Survey among Danish Oncologists.

Background Treatment patterns for cancer-associated venous thrombosis (CAT) has been shown to be nonconsistent with contemporary guideline recommendations, resulting in poor patient outcomes. Objectives The study aimed to describe contemporary CAT management in Danish oncology departments and identify knowledge gaps and inconsistencies between guidelines and clinical practice. Patients and Methods A survey questionnaire in Danish was developed based on contemporary national guidelines. Using an open recruitment strategy, invitations to participate in the electronic survey were sent to physicians employed at oncology departments in Denmark in winter of 2018/2019. The questionnaire was based on current national guidelines and included 10 items with multiple choices and a free-text option to specify or comment. The questionnaire was pilot-tested by a junior and senior oncologist. Results A total of 142 physicians completed the survey, representing all Danish geographical regions and various seniority. The majority reported that CAT was treated and followed up in oncology departments. However, 36.6% of the physicians were unaware of the existence of designated cancer thrombosis guidelines. Risk of venous thrombosis was generally assessed without diagnostic scores. Almost all (98.6%) reported low-molecular-weight heparin to be first-line treatment for CAT. Treatment duration seemed wrongly influenced by subtype of venous thrombosis, and 44.5% responded that thromboprophylaxis among hospitalized patients was substantially underused. Conclusion The variability in the daily clinical management of CAT demonstrated through this survey indicates a potential to increase awareness of available guidelines, standardized use of inpatient thromboprophylaxis, and organized treatment and follow-up in a multidisciplinary setting, which would potentially improve management of CAT in Denmark.

OC-16 Apixaban as treatment for cancer-associated venous thrombosis: the CAP study

OC-16 Apixaban as treatment for cancer-associated venous thrombosis: the CAP study

Cancer-Associated Venous Thromboembolism in Ambulatory Solid Organ Malignancy Patients: Experience from a Cancer Research Institute.

Cancer-associated deep venous thrombosis (DVT) and venous thromboembolism (VTE) are exceedingly common in patients with cancer. One-fifth of DVT events occur in patients with cancer and it is the second leading cause of death in patients with cancer after cancer itself. Data on DVT in cancer patients on medical therapy, especially from Indian experiences, are sparse. Here, we present our experience in ambulatory patients with solid organ cancer. The purpose of the study was to study the incidence of DVT in cancer patients on medical therapy and to analyze probable DVT risk factors. This study was a hospital-based single-arm retrospective collection and analysis of hospital records from patients receiving medical therapy on an outpatient and short-stay basis. From January 2016 to February 2017, adult solid organ cancer patients attending the medical oncology outpatient department (OPD), receiving active anticancer treatment, either oral or injectable, were included. The data was retrieved from the medical records department and the department of radiology. Descriptive statistics were used to analyze the data. Twenty-nine out of 1190 patients were documented to have developed DVT during the study period. The incidence of DVT in the outpatient settings was 2.4%, and DVT associated with venous access device in situ was seen in 4.05% (20/493) of the patients. Gynecological, breast, and hepatobiliary malignancies comprised most of the cases. Cancer patients are clearly at increased risk for DVT, but this risk is highly variable. It differs between subgroups of cancer patients. Five points Khorana risk model can predict risk for DVT in the ambulatory cancer patients receiving chemotherapy; however, the routine use of thromboprophylaxis in all cancer patients is not recommended. High-risk patients especially those with venous access devices need careful evaluation and counseling for prompt reporting and recognition of venous thrombosis.

Blocking podoplanin inhibits platelet activation and decreases cancer-associated venous thrombosis

BackgroundPatients with cancer are at a high risk of venous thromboembolism (VTE), studies have shown that high expression of podoplanin (PDPN) in tumors is associated with increased risk of VTE. MethodsTwo human malignant cell lines (NCI-H226 and C8161) expressing high levels of PDPN were selected to explore the role of platelet in cancer-associated venous thrombosis in vitro and in vivo. Immunohistochemical staining using anti-PDPN antibody was performed in the pulmonary carcinoma patients. ResultsBoth NCI-H226 and C8161 cells expressing high PDPN triggered platelet activation via CLEC-2 in vitro, which was abrogated by an anti-PDPN antibody SZ-168. Furthermore, the in vivo study revealed that injection of CHO-PDPN or C8161 in two mouse model of venous thrombosis activated platelets, increased platelet counts and enhanced thrombosis. More importantly, PDPN-enhanced thrombosis was reduced in mice treated with SZ168. A total of 63.3% tumor specimens stained positive for PDPN. High PDPN expression was associated with an increased risk of VTE and poor prognosis. ConclusionsPDPN expression in tumors induced platelet activation and was related to a high risk of VTE via platelet activation. SZ168 inhibited PDPN-induced platelet activation in vitro and decreased the incidence of VTE in mice.

Single-Drug Approach with Edoxaban is Effective for Resolving Non-Acute Cancer-Associated Venous Thrombosis: A Single-Arm Retrospective Analysis.

Recently, cancer-related venous thromboembolism (VTE) has been termed “cancer-associated thrombosis (CAT)” and is the focus of current research. We retrospectively investigated the efficacy of a single-drug approach with edoxaban for the treatment of non-acute CAT. Thirty-two non-acute CAT patients who received edoxaban were analyzed. The primary endpoint of this analysis was the thrombus disappearance rate at the first evaluation. Secondary endpoints included progression/recurrence of VTE, major bleeding, and D-dimer levels. The thrombus disappearance rate was 62.5%. Therefore, the null hypothesis for the primary endpoint (thrombus disappearance rate of ≤32.0%) was rejected (p = 0.00038) based on the rate of the previous study as the historical control. Recurrent VTE and major bleeding occurred in two patients each. After the start of treatment with edoxaban, a significant difference in D-dimer levels was observed (p = 0.00655). We demonstrated that a single-drug approach with edoxaban is a potential treatment option for non-acute CAT.