Treatment Of Venous Thromboembolism In Patients Research Articles

Venous thromboembolism treatment in patients with cancer: reflections on an evolving landscape

Cancer is a leading cause of morbidity and mortality worldwide. It is also one of the strongest risk factors for venous thromboembolism (VTE), reported in approximately 20% of all cases of VTE diagnosed. The thrombotic effect of cancer and its treatments, however, is highly variable among patients and changes over the course of their cancer. Anticoagulant therapy remains the cornerstone of VTE treatment, but it is associated with a substantial rate of VTE recurrence and the potential for serious bleeding. The risk of bleeding in patients with cancer is also dependent on the cancer type and its treatments, often revealing underlying tumor invasion of mucosal or parenchymal tissues, and treatment complications such as thrombocytopenia or coagulopathy. Over the past few decades, efforts to improve the efficacy and safety of anticoagulant therapy for the treatment and prevention of cancer-associated thromboembolism have resulted in changes in the standard of practice. This evolution has been made possible largely through the development of new anticoagulants. This review will reflect on the major advances in the treatment of cancer-associated thrombosis and offer insights on how to address unmet needs in this field.

Clinical Characteristics, Treatment, and Outcomes of Provoked Acute Cerebral Sinovenous Thrombosis in Patients

Background Cerebral sinus venous thrombosis (CSVT) is a rare pediatric condition with an estimated incidence of 0.7 per 100,000 children. However, amongst pediatric venous thromboembolism (VTE), the proportion of CSVT is high, at about 10% of all pediatric VTE. Key risk factors include perinatal stressors in cases of neonatal CSVT and acute infections, especially head and neck infections, in older children. To date, few multinational trials of pediatric VTE treatment have reported findings specifically among CSVT patients. Aims We sought to describe the clinical characteristics, treatment strategies, and outcomes of the patients with provoked acute CSVT enrolled in the Kids-DOTT trial and to compare these features to those of Kids-DOTT participants with non-CSVT VTE. Methods Kids-DOTT was an NIH-sponsored multinational randomized clinical trial (RCT) comparing 6 weeks vs. 3 months of anticoagulation for provoked acute VTE treatment in patients <21 years, with two non-randomized cohort arms run in parallel to the RCT for patients with persistent antiphospholipid antibodies or complete veno-occlusion at 6 weeks post-diagnosis of the index VTE. The primary RCT findings were recently published. In the present analysis, descriptive statistics were used to summarize patient and thrombus characteristics, treatments, and outcomes, and variables were compared between CSVT and non-CSVT VTE groups using Mann-Whitney U test for continuous variables and Chi-squared or Fisher's exact test, as appropriate, for categorical variables. All statistical analyses were performed using R Core Team, 2021. A P-value of <0.05 was considered statistically significant. Results Among 532 patients enrolled in the Kids-DOTT trial, the index VTE was a CSVT in 75 (14%). Age distribution differed significantly ( P=0.002) between CSVT and non-CSVT VTE patients, with the CSVT more likely to occur in neonates and children, compared to non-CSVT VTE more likely to occur in adolescents. CSVT was less likely to be CVC-related compared to non-CSVT VTE. The frequency of any infection (56.9% vs 26%, p<0.001) and specifically infection of the head/neck (35.4% vs 2%; P<0.001) as a provoking factor was significantly higher for CSVT vs. non-CSVT VTE. Non-head and neck infections were less likely to be associated with CSVT compared to non-CSVT VTE. One-third of CSVT patients received 6 weeks, while two-thirds received > 3 months, of anticoagulation (Table 2). No patients developed ISTH-defined symptomatic recurrent VTE or clinically relevant bleeding. Conclusions These multinational trial findings substantiate those of retrospective studies implicating head/neck infection as an important provoking factor for CSVT in young patients. The absence of recurrent VTE or clinically relevant bleeding among CSVT patients managed with anticoagulation in Kids-DOTT serve to augment recent RCT findings of CSVT treatment in children involving direct oral anticoagulants, demonstrating the safety and efficacy of therapeutic anticoagulation for pediatric CSVT.

NCOG-17. RETROSPECTIVE REVIEW OF THE TREATMENT OF VENOUS THROMBOEMBOLISM IN GLIOBLASTOMA PATIENTS RECEIVING BEVACIZUMAB

Abstract Patients with malignant gliomas have an inherently high risk of venous thromboembolism (VTE).1 Bevacizumab is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody commonly used in the treatment of recurrent high-grade gliomas and is known to increase the risk of VTE as well as intracranial hemorrhage.2 Anticoagulation (AC) for VTE also increases the risk intracranial hemorrhage in patients with malignant brain tumors.3 This makes the treatment of VTE in patients with GBM receiving bevacizumab therapy particularly challenging. Here we completed a single center retrospective chart review of patients with glioblastoma (GBM) treated concurrently with anticoagulation for VTE and bevacizumab therapy. The purpose of this review was to assess the safety of concurrent use of these therapies and to note any statistically significant difference in the incidence of hemorrhagic complications between patients treated with anticoagulation at therapeutic versus prophylactic dosing. METHODS: 144 patients with a diagnosis of high-grade glioma and were treated at UCI from 1/1/2019 through 1/1/2022 were screened for the study. 13 GBM patients on treatment with bevacizumab and concurrent anticoagulation were included. Clinical records of these patients were reviewed for the incidence of intracranial hemorrhage or any clinically significant bleeding. RESULTS: The incidence of ICH in GBM patients on concurrent therapy with bevacizumab and anticoagulation was 7.7% and the incidence of other minor bleeding complications was 7.7%. ICH and other minor bleeding was exclusively seen in patients on therapeutic anticoagulant dosing. No bleeding complications were noted in patients on prophylactic AC dosing. CONCLUSION: There is a risk of ICH in patients receiving both bevacizumab and anticoagulation, however compared to historical data, the incidence reported in our study is less than the incidence of ICH in GBM patients on anticoagulation alone. Our study suggests that it is relatively safe to treat patients with these therapies simultaneously.

The Role of Injectables in the Treatment and Prevention of Cancer-Associated Thrombosis.

Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the tremendous heterogeneity of clinical situations in patients with cancer and the challenges of CAT, there is no single universal treatment option for patients suffering from or at risk of CAT. Initial studies suggested that patients seemed to prefer an anticoagulant that would not interfere with their cancer treatment, suggesting the primacy of cancer over VTE, and favoring efficacy and safety over convenience of route of administration. Recent studies show that when the efficacy and safety aspects are similar, patients prefer the oral route of administration. Despite this, injectables are a valid option for many patients with cancer.

Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Obesity.

Background: Direct oral anticoagulants (DOACs) are known to have similar efficacy with a decreased risk of bleeding when compared to warfarin for the treatment of venous thromboembolism (VTE). In patients with obesity, there are limited data regarding the safety and efficacy of DOACs. Despite concerns for both under- and over-dosing patients with extremes of body weight, there are no dose adjustment recommendations in the package inserts for any of the DOACs. Objective: To evaluate the safety and efficacy of DOACs versus warfarin for the treatment of VTE in patients with obesity. Methods: This single-center, retrospective cohort study included obese patients initiated on DOAC or warfarin therapy for VTE from January 2015 to January 2022. Patients with cancer, hypercoagulable disorders, end-stage kidney disease, or pregnancy were excluded. The primary endpoint was VTE recurrence. Secondary endpoints included major and minor bleeding. Results: A total of 120 patients met criteria for inclusion. Ninety-two received DOAC therapy and 28 received warfarin. The primary endpoint occurred in 4 patients in the DOAC group and 3 patients in the warfarin group (P = 0.35). Major bleeding occurred in 2 patients. Minor bleeding events occurred in 10 (8.33%) patients. Of those, 6 (6.5%) events occurred in patients receiving a DOAC and 4 (14.3%) events occurred in patients receiving warfarin (P = 0.28). Limitations of this study include the retrospective single-center study design. Conclusions: There was a comparable risk of bleeding and recurrent VTE between DOACs and warfarin in patients initiated on therapy for VTE.

Cancer-associated thrombosis and drug-drug interactions of antithrombotic and antineoplastic agents.

Venous thromboembolism (VTE) is often associated with malignant diseases and notably contributes to morbidity and mortality in patients with cancer. Cancer-associated thrombosis (CAT) brings additional costs to health expenditures and has a negative impact on oncological outcomes. Either the recurrence rate of VTE or bleeding complications are also higher in patients with cancer. Prophylactic anticoagulation has been recommended in peri-surgical periods, inpatient settings, and high-risk ambulatory patients. Although various risk stratification scores are used, none are ideal for identifying patients who can benefit from anticoagulant prophylaxis. New risk scoring systems or biomarkers are needed to identify patients who are more likely to benefit from prophylaxis with low bleeding risk. The questions about the patients who will be given prophylaxis and those who develop thromboembolism, with which drug, and how long they will be treated are still not fully answered. Anticoagulation is the cornerstone of the treatment, but management of CAT remains complex. Low molecular weight heparins and direct oral anticoagulants are effective and safe options for the treatment of CAT. Recognizing adverse effects, drug-drug interactions, and accompanying conditions that cause dose adjustment is crucial. Prevention and treatment of VTE in patients with cancer require a multidisciplinary and patient-based approach. PLAIN LANGUAGE SUMMARY: Cancer-associated thrombosis is a significant cause of mortality and morbidity in patients with cancer. Chemotherapy, surgery, and/or use of central venous access remarkably increase the risk of thrombosis. Prophylactic anticoagulation should be considered not only in inpatient follow-up and during peri-surgical period but also ambulatory patients with a high risk of thrombosis. Many parameters, such as drug-drug interactions, primary side of cancer, and comorbidities of patients should be considered when selecting anticoagulant drugs. More accurate risk stratification scores or biomarkers are still an unmet need.

Safety and efficacy of apixaban versus low-molecular weight heparin or vitamin-K antagonists for venous thromboembolism treatment in patients with severe renal failure: A systematic review and meta-analysis

IntroductionChronic kidney disease is an independent risk factor for venous thromboembolism (VTE). Traditionally, Low Molecular Weight Heparin (LMWH) followed by warfarin has been the conventional therapy for VTE treatment. Direct oral anticoagulants (DOACs), including apixaban, have shown several advantages over the traditional therapy in individuals with normal kidney function. This meta-analysis aims to review the safety and efficacy of apixaban compared to warfarin or LMWH for the treatment of VTE in severe renal failure. MethodWe conducted literature search in PubMed, Embase, and Cochrane databases. Retrospective observational studies involving clinical effectiveness and safety outcomes of apixaban compared to warfarin in adult patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/m2 or on dialysis were included. ResultsEight studies were included in the analysis. Significant reduction in VTE recurrence observed in apixaban compared to warfarin (RR, 0.65; 95 % CI, 0.43–0.98; P = 0.04; I2 = 78 %). No significant difference in all-cause mortality between apixaban and warfarin (RR, 0.99; 95 % CI, 0.91–1.07; P = 0.74; I2 = 0 %). Apixaban showed a significantly lower rate of major bleeding (RR, 0.72; 95 % CI, 0.62–0.84; P < 0.0001; I2 = 34 %) and minor bleeding events (RR, 0.42; 95 % CI, 0.21–0.86; P = 0.02; I2 = 10 %) compared to warfarin. No significant difference observed in clinically relevant non-major bleeding between apixaban and warfarin (RR, 0.81; 95 % CI, 0.65–1.00; P = 0.05; I2 = 67 %). ConclusionApixaban was favored over warfarin for treating VTE in severe renal failure, reducing VTE recurrence and bleeding risk. No differences were observed in all-cause mortality and CRNMB events. More evidence is required due to limited RCTs and prospective studies.

Cancer-associated thrombosis during chemotherapy: treatment and prevention: A review

Cancer-associated thrombosis is a significant problem today for both oncologists and vascular surgeons. In patients with malignant neoplasms the incidence of symptomatic venous thromboembolism (VTE) is 47 times higher than in the general population. The presence of distant metastases in solid tumors increases the risk of VTE. Most often, VTE develop in pancreatic cancer and stomach cancer. Chemotherapy increases the risk of developing VTE. Low-molecular-weight heparin and direct oral anticoagulants are used for the treatment of VTE in patients with chemotherapy. The results of the СARAVAGGIO study demonstrated that apixaban is not inferior to dalteparin in the treatment of VTE in patients with active cancer and does not increase the risk of bleeding. Before starting chemotherapy, it is necessary to assess the risk of developing VTE using the Khorana risk score. Outpatient patients with high-risk cancer (Khorana score 2 before the start of a new systemic chemotherapy regimen) may be prescribed thromboprophylaxis with low molecular weight heparin. The idea of using direct oral anticoagulants seems promising, but so far it is beyond the scope of approved indications.

New Oral Anticoagulants Open New Horizons for Cancer Patients with Venous Thromboembolism.

Venous thromboembolism (VTE) is associated with increased morbidity and mortality, decreased quality of life, and higher economic burden in patients with cancer. Currently, the treatment of VTE in patients with cancer is particularly challenging. For many years, low molecular weight heparin (LMWHs) has been the standard for the treatment of cancer-associated VTE. Recently, the introduction of new oral anticoagulants (NOACs) may offer an oral anticoagulant option for some patients with cancer-associated thrombosis (CAT) as a growing body of literature supports the use of NOACs in the setting of CAT. With the use of NOAC as a new option in the management of CAT, clinicians now face several choices for the individual cancer patient with VTE. We need a more in-depth understanding of the drug properties, efficacy and safety, economic analysis that allows us to choose the most appropriate treatment for each patient. In the review, we will present an overview of CAT management, discuss the available evidence, economic costs for NOACs in the treatment of CAT, and seek to provide the best range of treatments for cancer patients.

Dabigatran Etexilate: A Review in Pediatric Venous Thromboembolism

Although rare in children, venous thromboembolism (VTE) is markedly more likely in hospitalized patients, particularly with the use of central venous access devices. Dabigatran etexilate (Pradaxa®) is one of the first direct non-vitaminK antagonist oral anticoagulants (DOAC) approved for use in pediatric patients. It is approved in the EU and USA for the treatment of VTE in patients who have been treated with a parenteral anticoagulant for ≥ 5 days, and for the prevention of recurrent VTE. In an open-label, phase2b/3 clinical trial in pediatric patients with acute VTE treated for ≈ 3months, dabigatran etexilate was non-inferior to standard of care (SOC) treatment for the primary composite endpoint of complete thrombus resolution, freedom from recurrent VTE and VTE-related death. In a single-arm phase3 safety study, few patients experienced recurrent VTE with ≤ 12months of anticoagulation with dabigatran etexilate. Dabigatran etexilate was generally well tolerated in both studies; bleeding events were mostly minor and, in the phase 2b/3 study, occurred at a similar incidence to SOC. Although further data will be useful, dabigatran etexilate is a valuable and convenient treatment option in pediatric VTE.

Anticoagulation as secondary prevention of massive lung thromboses in hospitalized patients with COVID-19

Anticoagulation as secondary prevention of massive lung thromboses in hospitalized patients with COVID-19

Direktni oralni antikoagulantni lekovi u prevenciji i lečenju tromboza povezanih sa tumorom

Patients with malignancy have higher risk of developing cancer-associated thrombosis (CAT), with predominance of venous thromboembolism (VTE). CAT in these patients leads to the delay of specific cancer treatment, worse treatment outcomes and also increased mortality rates. This article is evaluating the role of direct oral anticoagulants (DOAC) in the prophylaxis and treatment of VTE in patients with CAT. The review shed the light on the newest recommendations and guidelines, according to the newest treatment guidelines, but it also discusses the potential risks of DOAC therapy in patients with CAT. Compared to the previous recommendations, in the latest clinical guidelines for the prevention and treatment of CAT, DOAC are becoming more important. However, considering that cancer patients represent a highly specific group of patients, diversification and expansion of CAT anticoagulant therapy provides personalized approach to each patient achieving more efficient and safer profile of anticoagulant therapy.

Venous and arterial thromboembolism in patients with inflammatory bowel diseases.

The risk of thromboembolism (TE) is increased in patients with inflammatory bowel disease (IBD), mainly due to an increased risk of venous TE (VTE). The risk of arterial TE (ATE) is less pronounced, but an increased risk of cardiovascular diseases needs to be addressed in IBD patients. IBD predisposes to arterial and venous thrombosis through similar prothrombotic mechanisms, including triggering activation of coagulation, in part mediated by impairment of the intestinal barrier and released bacterial components. VTE in IBD has clinical specificities, i.e., an earlier first episode in life, high rates during both active and remission stages, higher recurrence rates, and poor prognosis. The increased likelihood of VTE in IBD patients may be related to surgery, the use of medications such as corticosteroids or tofacitinib, whereas infliximab is antithrombotic. Long-term complications of VTE can include post-thrombotic syndrome and high recurrence rate during post-hospital discharge. A global clot lysis assay may be useful in identifying patients with IBD who are at risk for TE. Many VTEs occur in IBD outpatients; therefore, outpatient prophylaxis in high-risk patients is recommended. It is crucial to continue focusing on prevention and adequate treatment of VTE in patients with IBD.

Evaluation of direct oral anticoagulant use for cancer-associated venous thromboembolism (VTE) in lung cancer.

243 Background: National Comprehensive Cancer Network recommends direct oral anticoagulants (DOACs) as preferred agents for treatment of cancer associated VTE in patients without gastric or gastroesophageal lesions. Currently at Massachusetts General hospital (MGH), DOACs are used in treatment of cancer associated VTE. This study was performed to evaluate the safety and efficacy of DOACs for treatment of VTE in patients with metastatic lung cancer. Methods: Retrospective chart review of patients at MGH with diagnosis of metastatic lung cancer who were prescribed edoxaban, rivaroxaban, or apixaban for treatment of VTE between January 2018 and January 2021 was performed. Patients were identified using electronic medical record reports. Data was collected on age, anticoagulation regimen, intent of anticoagulation therapy, presence of brain metastasis, renal function, liver function and platelet counts. The primary outcome was to assess the incidence of treatment failure, defined as VTE recurrence or major bleeding leading to a change in anticoagulation therapy. Results: 152 patients were evaluated, of which 57 received apixaban, 44 rivaroxaban, and 7 edoxaban. Most (n = 93) patients received enoxaparin for 14-90 days prior to transitioning to DOACs. Median age and creatinine clearance were 69 years and 63 mL/min, respectively. All patients had platelet count ≥ 50K/uL. Brain metastasis was present in n = 39 patients. Pulmonary embolism (PE)(n = 98), deep vein thrombosis (DVT) (n = 52), or both (n = 2) were the indication for DOAC therapy. Bleeding occurred in 14 patients including gastrointestinal bleeding (n = 5), hematuria (n = 4), epistaxis (n = 1), and hemoptysis (n = 4). Among patients with bleeding events, 7 received rivaroxaban and 7 received apixaban. Major recurrent VTE while on DOACs occurred in 5 of patients, including DVT (n = 2) and PE (n = 3). Patients with recurrent VTE received rivaroxaban (n = 7), apixaban (n = 3) and edoxaban (n = 1). All patient whom experienced bleeding and VTE were ≥ 60 years old. Brain metastasis was present in n = 2 of patients with bleeding events and n = 2 patients with recurrent VTE. Majority of patients (n = 93) received enoxaparin for 14-90 days prior to transitioning to DOACs. The median interval between initiation of DOACs and bleeding was 60 days (range 30-365) and recurrent VTE event was 90 days (range 60‐365). Conclusions: The results of this study suggest that outcomes of DOAC use for the treatment of cancer-associated VTE in patients with metastatic lung cancer are comparable to the results of large randomized controlled trials. DOAC therapy is a safe and effective anticoagulation option for lung cancer patients with cancer-associated thromboembolism.

Characteristics of Venous Thromboembolism in Patients with Acute Leukemia

Background: Malignancy-associated venous thromboembolism (VTE) is well described in the literature. Risk factors in this population include type of underlying malignancy, active chemotherapy, and central venous catheters. Despite this, there remains a paucity of data regarding leukemia-associated VTE in the adult population. Furthermore, treatment of VTE in patients with acute leukemia is based on expert opinion without standardization. We aim to describe the incidence and characteristics of VTE in patients with acute leukemia at our center, including the VTE treatments received.Methods: This is a retrospective chart review of all patients diagnosed with acute leukemia at The Ottawa Hospital (TOH) from January 2007 to September 2015. Details of patients' demographics, cytogenetics, and thrombosis characteristics were collected into a database. A VTE event was defined by either a positive diagnostic scan or a positive documentation. Thrombocytopenia was defined as a platelet count less than 50 x 109/L.Results: 440 patients with acute leukemia were identified. Of these, 41 patients (21 males and 20 females) developed 59 VTE events within the follow-up time, conferring a cumulative incidence of 9.3%. 12 out of 41 patients (29.3%) developed recurrent VTE. Of the 59 thrombotic events, 12 were pulmonary emboli, 46 were extremity deep venous thrombi, and 1 was portal vein thrombosis. 15 out of 41 (36.6%) patients had a VTE event while thrombocytopenic. Detailed characteristics of these patients are summarized in Table 1. Managements of these thrombotic events are summarized in Table 2. Of the 41 acute leukemia patients with VTE, there were 5 (12.2%) major bleeding events.Conclusion: Patients with acute leukemia have a high rate of venous thrombosis and a high rate of recurrence. Anticoagulation in this population is frequently complicated by thrombocytopenia due to underlying leukemia and chemotherapy. The optimal management of venous thrombosis in this population is not defined and remains variable as demonstrated by this analysis. Developing a standard management protocol for the prevention and treatment of VTE in this high risk population would be important in reducing the morbidity and mortality associated with VTE. [Display omitted] DisclosuresSabloff:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Current Recommendations for the Management of Cancer-Associated Venous Thromboembolism

Abstract Cancer-associated thrombosis (CAT) is a major cause of death in oncological patients. The mechanisms of thrombogenesis in cancer patients are not fully established, and it seems to be multifactorial in origin. Also, several risk factors for venous thromboembolism (VTE) are present in these patients such as tumor site, stage, histology of cancer, chemotherapy, surgery, and immobilization. Anticoagulant treatment in CAT is challenging because of high bleeding risk during treatment and recurrence of VTE. Current major guidelines recommend low molecular weight heparins (LMWHs) for early and long-term treatment of VTE in cancer patients. In the past years, direct oral anticoagulants (DOACs) are recommended as potential treatment option for VTE and have recently been proposed as a new option for treating CAT. This manuscript will give a short overview of risk factors involved in the development of CAT and a summary on the recent recommendations and guidelines for treatment of VTE in patients with malignancies, discussing also some special clinical situations (e.g. renal impairment, catheter-related thrombosis, and thrombocytopenia).

Evaluation of cabozantinib (cabo) in combination with direct oral anticoagulants (DOAC) or low molecular weight heparin (LMWH) in renal cell carcinoma (RCC).

291 Background: Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. Despite cabo improving RCC outcomes, VTE management in these patients remains a challenge, partly due to poor understanding of cabo safety profile and drug interactions with anticoagulants. Recent anti-Xa DOAC studies demonstrated comparable efficacy and safety with LMWH for VTE treatment in patients with cancer. Thus far, cabo clinical trials have largely allowed concurrent LMWH use but not DOACs. Herein, we investigated the hemostasis safety profile of cabo with different anticoagulants in patients with RCC. Methods: We performed a retrospective multicenter study (7 sites) of patients with advanced RCC receiving treatment with cabo. Patients were allocated into three groups: cabo with concomitant use (at least 1 week) of 1) DOACs (anti-Xa inhibitors), 2) LMWH, or 3) no anticoagulant. Primary endpoint was to evaluate the rate of major bleeding events (defined per the International Society of Hemostasis and Thrombosis criteria) in the above groups. Secondary endpoint was rate of new/recurrent VTE while on anticoagulation. Overall comparison between groups was analyzed by Fisher exact test. If a difference was found, then pairwise comparison was done. Results: Between 2016-2020, 172 patients with RCC received cabo (DOAC 50, LMWH 18, and no anticoagulant 104). At initiation, cabo median dose was 60 mg but 45% had dose reduction. Median age was 63 [IQR 57-69]. Most were males (77%), had clear cell histology (81.5%), underwent nephrectomy (76.7%), and had intermediate IMDC risk disease (59%). Cabo was first, second, and subsequent line of therapy in 19.8%, 34.9%, and 45.3% of patients, respectively. The table below shows major bleeding and VTE events between groups. An overall difference of major bleeding was found between the three groups comparison ( p=0.009). There was no difference in major bleeding events between patients who received DOAC vs LMWH ( p=0.28) and DOAC vs no anticoagulant ( p=0.1) but there was a difference between LMWH vs no anticoagulant ( p=0.02). Two patients died from bleeding (one in LMWH and one in DOAC group). Conclusions: This study highlights the first reported real world experience of cabo with different anticoagulants in patients with advanced RCC. Cabo use with a DOAC had a similar bleeding risk in comparison to patients not receiving any anticoagulation. In carefully selected patients, DOACs can be considered as concurrent medications in those receiving cabo. Given the low number of patients receiving LMWH, it is difficult to draw conclusions from this group. Data are currently being updated to expand subjects receiving DOAC and LMWH in our cohort. [Table: see text]

Venous thromboembolism in patients with inflammatory bowel disease: review of literature and practical algorithms.

Inflammatory bowel disease (IBD) is associated with several extra-intestinal complications, including venous thromboembolism (VTE). In patients with IBD, VTE occurs at younger age and is associated with higher recurrence and mortality rates as compared to patients without IBD. The risk appears to be higher during active disease and hospitalization. In this review we target the importance of prophylaxis and aim to describe strategies for treatment of VTE in patients with IBD. More awareness is needed, given the fact that VTE is often preventable with appropriate pharmacological prophylaxis. Algorithms are provided on which patients should be given prophylaxis and on treatment duration of VTE in patients with inflammatory bowel disease.

Cancer-Associated Venous Thromboembolism Treatment With Anti-Xa Versus Weight-Based Enoxaparin: A Retrospective Evaluation of Safety and Efficacy.

Venous thromboembolism (VTE) is a complication of cancer, for which low-molecular-weight heparin (LMWH) remains the preferred anticoagulant. Enoxaparin is traditionally dosed using weight. In certain populations, monitoring anti-Xa levels for therapeutic effect provides pharmacokinetic guidance for dose adjustments. There is a paucity of data regarding anti-Xa-directed enoxaparin dosing for treatment of VTE in patients with cancer. This study aims to evaluate efficacy (recurrent VTE) and safety (major bleed) between enoxaparin anti-Xa-guided dose adjustments and weight-based dosing in patients with cancer-associated VTE. This single-center, retrospective cohort study examined patients treated with enoxaparin for cancer-associated VTE using data from electronic health records. There were 674 patients who met the inclusion criteria, with 283 receiving anti-Xa-directed dose adjustments. Recurrent VTE, major bleed, or all-cause death occurred in 102 of 283 patients (36%) in the anti-Xa cohort and 166 of 391 patients (42.5%) in the weight-based cohort (hazard ratio [HR] = 0.73; 95% CI = 0.57-0.93; P = 0.01). When death was removed from the composite end point, there was no significant difference between the cohorts in recurrent VTE or major bleed (HR = 1.18; P = 0.38). In the anti-Xa cohort, a total of 1584 anti-Xa peak levels were collected, with 1324 (83.6%) drawn correctly in relation to enoxaparin administration. Of those, 714 (53.9%) were within therapeutic range. Patients with cancer receiving anti-Xa-guided enoxaparin dose adjustments for initial VTE, compared with weight-based dosing, had no significant difference in the rate of recurrent VTE or major bleed.

A systematic review of antithrombotic treatment of venous thromboembolism in patients with myeloproliferative neoplasms.

Patients with myeloproliferative neoplasms (MPNs), polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have an increased risk of thrombosis. Risk of recurrent thrombosis can be reduced with antithrombotic therapy and/or cytoreduction, but the optimal long-term management in patients with MPN with a history of venous thromboembolism (VTE) is unknown, and clinical practice is heterogeneous. We performed a systematic review and meta-analysis of randomized trials and observational studies evaluating anticoagulant and/or antiplatelet therapy, with or without cytoreduction, in MPN patients with a history of VTE. A total of 5675 unique citations were screened for eligibility. No randomized trials were identified. Ten observational studies involving 1295 patients with MPN were included in the analysis. Overall, 23% had an arterial or recurrent venous thrombotic event on follow-up. The recurrence risk was lowest for patients on oral anticoagulation plus cytoreduction (16%); 55 of 313 (18%) with vitamin K antagonists (VKA) and 5 of 63 (8%) with direct oral anticoagulants (DOACs). In 746 analyzed patients, the risk of recurrent VTE ranged up to 33% (median 13%) and was low in 63 DOAC plus cytoreduction-treated patients (3.2%). All types of antithrombotic treatments were associated with a lower risk of recurrent VTE when combined with cytoreduction. Most studies had a high risk of bias, whereas clinical and statistical heterogeneity led to inconsistent and imprecise findings. In summary, evidence on the optimal antithrombotic treatment of VTE in patients with MPN is based on observational studies only with low certainty for all strategies. Our data suggest that a combination of anticoagulation and cytoreduction may provide the lowest recurrence risk.