Acute Venous Thromboembolism In Patients Research Articles

Direct Oral Anticoagulants in The Treatment Of Acute Venous Thromboembolism in Patients With Obesity: A Systematic Review With Meta-Analysis

Direct Oral Anticoagulants in The Treatment Of Acute Venous Thromboembolism in Patients With Obesity: A Systematic Review With Meta-Analysis

Acute venous thromboembolism in patients with brain cancer: clinical course

BackgroundPatients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH). ObjectivesThe aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer. MethodsThis was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome. ResultsOverall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors. ConclusionIn patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

Healthcare utilization differences between an apixaban-based and warfarin-based strategy for acute venous thromboembolism in patients with end-stage kidney disease

IntroductionEvidence suggests that an apixaban-based strategy to treat acute venous thromboembolism (VTE) in patients with End-Stage Kidney Disease (ESKD) may be safer than a warfarin-based strategy. Apixaban has an additional advantage of not requiring bridging with heparin which often necessitates long hospitalizations for patients with ESKD. We sought to determine if an apixaban-based strategy is associated with less healthcare utilization than a warfarin-based strategy. Material and methodsWe employed a new-user, active-comparator retrospective cohort study using inverse probability of treatment weights (IPTW) to adjust for confounding demographic and clinical variables. Patients with ESKD newly initiated on either apixaban or warfarin for an acute VTE between 2014 and 2018 in the United States Renal Data System were included. Outcomes were presence of index hospitalization, length of index hospitalization, total hospital days, total hospital days excluding index hospitalization, total emergency department (ED) visits that did not result in hospitalization, and total skilled nursing facility days. ResultsAt six months, patients who received apixaban were less likely to have an index hospitalization, had a shorter index hospitalization (median of 4.0 vs 8.0 days, p < 0.001), and had fewer total hospital days. The IPTW and index year-adjusted incidence rate ratios of total hospital days at one, three, and six months were 0.83 (95 % confidence intervals (CI) 0.79–0.86), 0.84 (95 % CI 0.81–0.88), and 0.88 (95 % CI 0.83–0.92) for apixaban compared to warfarin. ConclusionAmong patients with ESKD and VTE, resource utilization for an apixaban-based strategy appears to be lower than for a warfarin-based strategy.

Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study.

Patients with end-stage kidney disease (ESKD) are at significantly increased risk for both thrombosis and bleeding relative to those with normal renal function. The optimal therapy of venous thromboembolism (VTE) in patients with ESKD is unknown. To compare the safety and effectiveness of apixaban relative to warfarin in patients with ESKD and acute VTE. New-user, active-comparator retrospective United States population-based cohort with inverse probability of treatment weighting, using the United States Renal Data System data from 2014 to 2018. We included adults with ESKD on hemodialysis or peritoneal dialysis who were newly initiated on apixaban or warfarin for an acute VTE. The coprimary outcomes were major bleeding, recurrent VTE, and all-cause mortality within 6 months of anticoagulant initiation. Secondary outcomes were intracranial hemorrhage and gastrointestinal bleeding. The primary analyses were based on intent-to-treat defined by the first drug received and accounted for competing risks of death. Sensitivity analyses included varied follow-up time, as-treated analyses, and dose-specific apixaban subgroups. The apixaban and warfarin cohorts included 2302 and 9263 patients, respectively. Apixaban was associated with a lower risk of major bleeding (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.70-0.94), intracranial bleeding (HR 0.69, 95% CI 0.48-0.98), and gastrointestinal bleeding (HR 0.82, 95% CI 0.69-0.96). Recurrent VTE and all-cause mortality were not significantly different between the groups. Apixaban was associated with a lower risk of bleeding relative to warfarin when used to treat acute VTE in patients with ESKD on dialysis.

Direct oral anticoagulants versus low-molecular-weight heparins for the treatment of acute venous thromboembolism in patients with gastrointestinal cancer: a systematic review and meta-analysis

BackgroundThe association between gastrointestinal (GI) cancer and a high incidence of venous thromboembolism (VTE) is well known. Previous randomized controlled studies demonstrated that direct oral anticoagulants (DOACs) effectively treat cancer-associated thrombosis (CAT). However, some DOACs appeared to increase the risk of bleeding, particularly in patients with GI malignancies. Therefore, the current systematic review and meta-analysis were conducted to evaluate the safety and efficacy of DOACs in GI cancer-associated thrombosis.MethodsTwo investigators individually reviewed all studies that compared DOACs and low-molecular-weight heparins (LMWHs) in GI cancer-associated thrombosis and were published in MEDLINE and EMBASE before February 2022. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel–Haenszel method.ResultsA total of 2226 patients were included in the meta-analysis. The rates of major bleeding in the DOAC and LMWH groups were not significantly different (relative risk [RR]: 1.31; 95% CI: 0.84–2.04; P = 0.23; I2 = 41%). However, the rate of clinically relevant nonmajor bleeding (CRNMB) was significantly higher in the DOAC group (RR: 1.76; 95% CI: 1.24–2.52; P = 0.002; I2 = 8%). The risks of recurrent VTE in the groups did not significantly differ (RR: 0.72; 95% CI: 0.49–1.04; P = 0.08; I2 = 0%).ConclusionsThe current data suggest that treatment of GI cancer-associated thrombosis with DOACs significantly increases the risk of CRNMB. However, the risk of major bleeding was not significantly different. The efficacy of DOACs for preventing recurrent VTE in GI cancer was comparable to that of LMWHs.Trial registrationINPLASY202180113.

Emergency Department Management of Acute Venous Thromboembolism in Patients With Obesity With Intravenous Unfractionated Heparin and Anti-Xa Monitoring

Background: Unfractionated heparin (UFH) remains a frequently utilized agent in the emergency department (ED) for management of acute venous thromboembolism (VTE). While various protocols of UFH dosing have been proposed for patients with obesity, the optimal dosing and monitoring strategy is unclear. Objective: This study aims to compare the time to the first therapeutic anti-Xa level in obese acute VTE patients following the use of either total body weight (TBW) or adjusted body weight-based (AdjBW) dosing of UFH in the ED, and to analyze the impact of different dosing strategies on patient outcomes. Methods: Inclusion criteria included adult patients with a BMI > 30 kg/m2, and suspected VTE managed with UFH per institutional protocol utilizing a bolus dose followed by maintenance infusion and anti-Xa monitoring. The primary outcome was time to the first therapeutic anti-Xa level in the group dosed per TBW compared with the group dosed per AdjBW. Safety outcomes included incidence of bleeding events, protamine administration, and mortality. Results: There were 32 patients included in the study. Patients dosed per TBW achieved a median time to first therapeutic anti-Xa level of 14.5 hours compared with 15 hours in the AdjBW group (P = .613). The median therapeutic UFH infusion rate was 16 units/kg/hr in the TBW group compared with 13.5 units/kg/hr in the AdjBW group (P < .001). Safety outcomes were not significantly different between groups. Conclusion: Patients presenting to the ED with acute VTE may be managed with UFH using either a TBW or AdjBW dosing strategy.

Cellular Indices and Outcome in Patients with Acute Venous Thromboembolism.

BackgroundCellular indices provide integrative information about systemic inflammation status which is readily available from routine laboratory parameters. This study aimed to evaluate the prognostic role of three cellular indices in patients with venous thromboembolism (VTE).MethodsThe RIETE registry database was used to determine the association between the baseline neutrophil-to-lymphocyte-ratio (NLR), platelet-to-lymphocyte-ratio (PLR) and systemic-immune-inflammation-index (SII) for 90-day adverse outcomes in patients with acute VTE.ResultsFrom January 2020 to April 2021, 4487 patients with acute VTE were recruited in the RIETE registry. Of these, 2683 presented with symptomatic pulmonary embolism (PE); 283 with incidental PE; 1129 with lower-limb deep vein thrombosis (DVT); 175 with upper-limb DVT; 69 with splanchnic vein thrombosis; 142 with superficial vein thrombosis and 20 with retinal vein thrombosis. Mean values were: NLR 5.9 ± 7.1, PLR 190 ± 158 and SII 1459 ± 2028. During the first 90-days, 38 patients (0.8%) developed recurrent DVT, 45 (1.0%) had recurrent PE, 152 (3.4%) suffered major bleeding, and 484 (11%) died. On multivariable analysis, patients with NLR >4.41 were at an increased risk for major bleeding and patients with NLR >4.96 were at the risk of death, while those with SII >1134.5 were at increased risk for death.ConclusionsThis study reports the results of a large cohort to date which evaluate the prognostic value of three cellular indices simultaneously in patients with acute VTE. Results support that none of the three baseline cellular indices were sufficient for prediction of VTE recurrences in acute VTE patients. The patients with higher baseline NLR values were at an increased risk of major bleeding or death, those with high SII values were only at an increased risk for mortality.

Abstract 10854: Acute Venous Thromboembolism in Patients with Elevated Body Mass Index, Can We Prescribe Direct Oral Anticoagulants

Background: Due to the efficacy and lower bleeding risk of direct oral anticoagulants (DOACs) compared to coumadin, they are becoming the treatment of choice for acute venous thromboembolism (VTE). There is limited data in using DOAC’s for treatment of VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE)) in patients with morbid obesity (body mass index &gt;40 kg/mm 2 ). We conducted a retrospective study to examine the rates of recurrence (failure of treatment) in patients diagnosed with an acute VTE. Methods: Electronic health record (EHR) from 8 hospitals in the Beaumont Health system were queried. A retrospective review of patients &gt; 18 years old with morbid obesity who were diagnosed with a DVT or PE and treated with a DOAC (rivaroxaban, apixaban or dabigatran) from 2010 to 2020 was performed. Individual charts were reviewed for ultrasound as well as computed tomography angiography results confirming the presence of an acute or chronic DVT or pulmonary embolism. To assess for recurrence, imaging studies performed 3 months after original diagnosis were studied. Results: 461 patients were included. The mean age was 58.9 years old with a range of 18-88 years old. Majority of patients were female (65.9%). The mean BMI was 46.5 with standard deviation of 7.4. 337 (73.1%) had an acute diagnosis of DVT or PE. When reassessing imaging 3 months after original diagnosis, only 2 (0.6%) patients had findings of recurrence (formation of new DVT or PE). Conclusion: In patient with morbid obesity, DOACs appear to be an effective therapy for treatment of DVT and PE. Further prospective studies are needed to confirm the findings of this analysis.

Management of acute venous thromboembolism in patients taking antiplatelet therapy

BackgroundConcomitant anticoagulant and antiplatelet therapy increases bleeding risk, but most data are derived from patients with atrial fibrillation. Patients with venous thromboembolism (VTE) may differ. ObjectiveTo study the management of patients diagnosed with acute VTE while receiving antiplatelet treatment. The primary outcome was the number of patients discharged with concomitant therapy. Secondary outcomes were clinically relevant bleeding, cardiovascular events, recurrent VTE and death during follow-up, according to discharge therapy. MethodsWe performed a post-hoc analysis of patients included in two prospective registries, sharing the same case report form, from 2007 to 2017. ResultsAmong the 1694 identified patients, 254 (15.0%) were receiving antiplatelet treatment at VTE diagnosis, of whom 61 (24.0%) were discharged with concomitant anticoagulant and antiplatelet therapy. In multivariable analysis, age ≥ 80 years-old and the use of Direct Oral Anticoagulants for VTE therapy were associated with the decision to stop the antiplatelet, while having dual anti-platelet therapy at baseline, a history of coronaropathy or peripheral arterial disease were associated with concomitant anticoagulant and antiplatelet therapy. The decision to stop antiplatelet was associated with a non-significant 46% decrease in the risk of bleeding (OR 0.54 (0.16; 1.78)), and a non-significant 68% increase in the risk of cardiovascular events (OR 1.68 (0.44; 6.46)). ConclusionAt acute VTE diagnosis, over 15% of patients were receiving antiplatelet agents, of whom 24% were discharged with concomitant anticoagulant and antiplatelet therapy. This therapeutic decision may be associated with a lower risk of cardiovascular events, but an increased risk of bleeding.

Long-Term Rivaroxaban for the Treatment of Acute Venous Thromboembolism in Patients with Active Cancer in a Prospective Multicenter Trial: KVTE13-01

BackgroundCancer patients with venous thromboembolism (VTE) are at a substantial risk of recurrent VTE despite anticoagulation therapy. Limited data is available regarding the effectiveness and safety of rivaroxaban in patients with active cancer and associated VTE.MethodsThis prospective, multicenter, open-label study enrolled patients with active cancer and newly diagnosed, objectively confirmed, lower-extremity deep vein thrombosis (DVT), pulmonary embolism (PE) or both between November 2013 and June 2016. Active cancer was defined as a histologically confirmed maligancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/metastatic cancer. Patients received rivaroxaban 15mg twice daily for the first 3 weeks, followed by 20mg once daily for 6 months. The primary objective of this study was to assess the symptomatic, recurrent VTE events following rivaroxaban treatment. The secondary objectives included any recurrent VTE events, bleeding complications (major or non-major clinically relevant [NMCR] bleeding events), and overall mortality. Blinded central adjudication was performed for all recurrent VTEs, bleeding events, and deaths. The recurrent VTE and bleeding events were calculated using a cumulative incidence method that incorporated death from any cause as competing risk. The study was registered at www.clinicaltrials.gov as #NCT01989845.Results127 patients were screened from 9 centers in Korea. Of these, 3 patients were not enrolled because they did not meet the eligibility criteria. Thus, 124 patients were enrolled. Mean age was 67 years (range, 28-85) and 55 (44%) were female. 27 patients (22%) had baseline ECOG performance status of 2. The most common primary tumor sites were lung (N=30, 24%), colorectum (N=24, 19%), pancreaticobiliary tract (N=16, 13%), stomach (N=16, 13%); 14 patients (11%) had hematologic malignancies. 93 patients (75%) had metastatic disease and 110 (89%) were under cancer treatments (chemotherapy and/or radiation). The qualifying thrombotic event was PE ± lower-extremity DVT in 102 patients (82%) and presented as symptomatic in 78 patients (63%).During the 6-month study period, 7 patients (fatal PE, 4; non-fatal PE, 3) experienced symptomatic recurrent VTE (cumulative rate, 5.9%, Figure 1). There were 2 patients with incidental recurrent PE. Thus, cumulative rate of any recurrent VTE was 7.6%. Major bleeding events occurred in 6 patients (cumulative rate, 5.3%; Figure 2) and NMCR bleeding events in 11 (cumulative rate, 10.2%). 28 patients died during the study period (cumulative rate, 24.0%; Figure 3).ConclusionRivaroxaban appears to be an effective and safe treatment in patients with cancer-associated VTE. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Ilio-femoral venous thrombosis with hereditary antithrombin deficiency: a case report of rare thrombotic disease and successful treatment with catheter directed thrombolysis

BackgroundHereditary antithrombin (AT) deficiency is an uncommon autosomal dominant thrombogenic disorder, which can cause venous thromboembolism (VTE). Although conservative treatment options for hereditary AT deficiency-associated VTE such as anticoagulation (warfarin, direct oral anticoagulant, or heparin), intravenous thrombolysis, and recombinant AT are well known, interventional treatment options have not been reported so far.Case summaryA 19-year-old man with a family history of thrombogenic diseases, referred to our hospital with left leg pain, was diagnosed with AT deficiency-associated VTE. In the absence of symptomatic relief with intravenous thrombolysis and anticoagulation, he received venous intervention and catheter directed thrombolysis (CDT) for 4 days for left iliac venous thrombosis. Following a second venous intervention, venous thrombus disappeared almost entirely on cross-sectional imaging, and his symptoms improved. He was discharged on apixaban and has been recurrence-free for one and a half years.DiscussionThis case presents CDT and maintenance therapy with apixaban as possible treatment options for VTE in patients with hereditary AT deficiency, especially following failure of conservative therapy. Individual risks and benefits should be considered when CDT is performed for acute VTE in patients with AT deficiency.

Direct oral anticoagulants in the treatment of acute venous thromboembolism in patients with obesity: A systematic review with meta-analysis

BackgroundDirect oral anticoagulants’ (DOAC) pharmacokinetics are affected by obesity. Their efficacy and safety in obesity (BMI≥30 kg/m2) and morbid obesity (BMI≥40 kg/m2) are still unclear in the treatment of venous thromboembolism (VTE). ObjectivesTo compare the efficacy/safety of DOAC versus vitamin K antagonist (VKA)/low molecular weight heparin (LMWH) for the treatment of VTE in patients with obesity and morbid obesity. The primary efficacy/safety outcomes were VTE recurrence and major bleeding (MB). Clinically relevant non-MB and mortality were also evaluated. MethodsA systematic literature search (MEDLINE, EMBASE, CENTRAL, Web of Science) identified studies evaluating DOAC in the treatment of VTE in patients with obesity and reporting one of the outcomes. Relative risks (RR) and 95 % confidence intervals (CI) were estimated using the Mantel-Haenszel method. ResultsWe included 21 studies (50,360pts) of which 16,150 patients had a BMI≥30 kg/m2 and 6443 patients had a BMI≥40 kg/m2. VTE recurrence was similar with DOAC compared to VKA/LMWH in patients with obesity (RR 1.03;95 %CI 0.93–1.15;p = 0.55) and morbid obesity (RR 1.06;95 %CI 0.94–1.19;p = 0.35). DOAC were also associated with a reduction in MB (RR 0.57;95 %CI 0.34−0.94;p = 0.03 and RR 0.71;95 %CI 0.50–1.00;p = 0.05 in patients with obesity and morbid obesity, respectively). Subgroup analyses comparing randomized controlled trials to observational studies showed consistent results. No difference was observed in regards of clinically relevant non-MB and mortality. ConclusionThere is no signal for differences in VTE recurrence in patients with obesity and morbid obesity treated with DOAC compared to VKA/LMWH, while DOAC likely reduce the risk of MB compared to VKA/LMWH.

Anticoagulant Usage Patterns for Acute Venous Thromboembolism in Patients with Advanced Liver Disease

Introduction: Management of acute venous thromboembolism (VTE) in patients with chronic liver diseases is challenging due to the risk of bleeding and thrombotic complications. No clinical trials have studied vitamin K antagonists (VKA) or low molecular weight heparins (LMWH) use in this population. Pivotal clinical trials evaluating direct oral anticoagulants (DOAC) such as apixaban, edoxaban, rivaroxaban, and dabigatran lead to the U.S. Food and Drug Administration approval for VTE treatment but these studies excluded patients with clinically significant liver disease. Methods: We conducted a single-center retrospective chart review of anticoagulant practice patterns in adult patients with cirrhosis (Child-Pugh Class A-C) diagnosed with acute VTE managed between January 1, 2010 through January 2, 2020. Acute VTE was defined as pulmonary embolism, deep vein thrombosis (DVT), and splanchnic vein thrombosis (SVT), which included portal vein thrombosis (PVT). Primary outcomes were recurrent VTE, bleeding events, and anticoagulant practice patterns and were calculated in the study population, as well as a subset excluding patients with only PVT. Cirrhosis, VTE, and bleeding diagnoses were based on ICD-9 and ICD-10 codes. Anticoagulant prescribing patterns were recorded in both the inpatient and outpatient setting, along with demographic, VTE risk factors, and key laboratory data. Baseline laboratory data were determined as the closest measured lab ≤180 days from the acute VTE diagnosis date. Child-Pugh score was calculated using the closest laboratory data and ICD-9 and ICD-10 codes ±180 days from the VTE diagnosis date. Anticoagulant usage was considered if ≥1 dose was administered. Statistical analysis was performed using SAS® version 9.4. Results: Baseline characteristics of the 1335 patients in the study are listed (Table 1-3). Median age was 65 years (range 19-98) with 845 male patients (63.3%). Following acute VTE, 467 patients (35.0%) received therapeutic anticoagulation, 114 patients (8.5%) received prophylactic anticoagulation, and 754 patients (56.5%) did not receive anticoagulation. Of patients that received therapeutic anticoagulation, 78 received apixaban, 1 received argatroban, 2 received bivalirudin, 7 received dabigatran, 1 received dalteparin, 0 received edoxaban, 180 received therapeutic enoxaparin, 19 received therapeutic fondaparinux, 231 received unfractionated heparin, 28 received rivaroxaban, and 159 received warfarin. Of patients that received prophylactic anticoagulation, 59 received enoxaparin, 10 received fondaparinux, and 246 received heparin. Of 599 patients with acute VTE without PVT only, 287 patients (47.9%) received therapeutic anticoagulation, 64 patients (10.7%) received only prophylactic anticoagulation, and 248 patients (41.4%) did not receive any anticoagulation. Many patients received more than one type of anticoagulant. Therapeutic anticoagulant usage patterns by year are depicted (Figure 1-2). Recurrent VTE occurred in 329 of all patients (24.6%). Recurrent VTE occurred in 196 of 467 patients (42.0%) on therapeutic anticoagulation, 33 of 114 patients (28.9%) on prophylactic anticoagulation, and 100 of 754 patients (13.3%) who did not receive any anticoagulation. Bleeding occurred in 721 of all patients (54.0%). Bleeding occurred in 288 of 467 patients (61.7%) on therapeutic anticoagulation, 67 of 114 patients (58.8%) on prophylactic anticoagulation, and 366 of 754 patients (48.5%) who did not receive any anticoagulation. Conclusion: Management of anticoagulant medications in patients with advanced liver disease has marked practice variation. Anticoagulant usage patterns changed over time with the approval of DOACs and increasing familiarity with these drugs. VKA and LMWH usage appeared to decrease over time as DOAC usage rose. Close to half of all patients did not receive any anticoagulation, even when excluding patients with only PVT from the population due to the common practice of monitoring PVT patients without anticoagulation. Further analysis of recurrent VTE and bleeding events based on individual anticoagulant medications and rationale for prescribed anticoagulant regimens is underway. We hope these findings will guide and encourage future studies evaluating safety and efficacy of anticoagulant medications in patients with advanced liver disease and VTE. Disclosures Kelkar: Acorn AI by Medidata, a Dassault Systemes Company: Current Employment. Rajasekhar:Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kedrion Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Octapharma Plasma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Baxter: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Characterization of Thrombin Generation Curve Shape in Presence of Platelets from Acute Venous Thromboembolism Patients.

Background. Anticoagulant therapy, the cornerstone treatment in acute venous thromboembolism (VTE), strongly impacts thrombin generation (TG). Until now, the appearance of the TG curve in platelet rich plasma (PRP) from patients with acute VTE has not been investigated. Methods. We analyzed the shape of TG curves measured in PARP of 180 acute VTE patients. Results. Normal shape of TG curves was observed in 110 patients, 50 patients showed no TG and 20 patients showed biphasic TG curve. The linear regression analysis, adjusted for age, sex, VTE clinical phenotypes and therapy showed that the appearance of biphasic curves is significantly associated with female sex, presence of cancer and therapy with Factor Xa inhibitors. Conclusions. This study demonstrated that despite taking anticoagulants, TG in presence of platelets is still present in the majority of acute VTE patients. Appearance of unusual TG curves is strongly related to the intake of anti-Factor Xa inhibitors. The clinical relevance of biphasic TG curve appearance requires further investigation.

Risk factors and clinical features of hospital-associated venous thromboembolism

Objective: To investigate the clinical features and risk factors of hospital-associated venous thromboembolism (VTE). Methods: The study enrolled acute VTE patients admitted into China-Japan Friendship Hospital from January 1, 2017 to December 31, 2017. The hospital-associated VTE (HA-VTE) group and the community-associated VTE (CA-VTE) group were classified according to whether the VTE occurred during hospitalization or within a 90-day period of admission to hospital (including inpatient with at least two days of hospital stay or a surgical procedure under general or regional anaesthesia). Differences in clinical features, risk factors, and mortality rate were compared between the two groups. Results: A total of 437 patients with acute VTE were analyzed in the study. Among them, 266 patients were HA-VTE, 171 patients were CA-VTE. Patients in the CA-VTE group were more likely to have varicose veins, sedentary, long-distance travel, and patients in the HA-VTE group were more complicated with recent surgery (<1 month), bed rest, active malignant tumor, acute infections, acute cerebral infarction, fracture, central venous catheter (P<0.05). The CA-VTE group had more clinical symptoms such as lower extremity pain, dyspnea, chest pain and chest tightness (P<0.05). HA-VTE patients had less clinical symptoms but were more severe than the CA-VTE patients, with more sudden deaths (0 vs 3.4%, P=0.035). Among HA-VTE patients, 92.8% experienced VTE during hospitalization or within 1 month of the preceding hospital encounter, with a 13-day median time to VTE. The all-cause mortality rate was higher for HA-VTE group than CA-VTE group (8.3% vs 1.2%, P<0.001), and the in-hospital VTE was more common compared to VTE diagnosed post-discharge (12.2% vs 3.4%, P<0.001). Conclusions: More than half events of VTE are related to recent hospitalizations. HA-VTE has different risk factors from CA-VTE, combined with fewer clinical symptoms but higher all-cause mortality rate. More attention about VTE should be paid to hospitalized patients to reduce the incidence of HA-VTE events.

Baseline Characteristics and Clinical Outcomes from the Cancer Associated Thrombosis - Patient Reported Outcomes with Rivaroxaban (COSIMO) Trial

Background: Patients living with cancer who develop venous thromboembolism (VTE) have a high risk of VTE recurrence, and traditional anticoagulants (low molecular weight heparin [LMWH] or vitamin K antagonists [VKAs]) are associated with significant treatment burdens. Rivaroxaban is a direct oral anticoagulant (DOAC) that may provide a more convenient treatment option for these patients. Methods: The COSIMO study was a multinational, prospective, non-interventional, single-arm cohort study designed to collect real-world data on patient treatment satisfaction and outcomes associated with rivaroxaban treatment following ≥4 weeks of LMWH/VKA therapy for the treatment of acute VTE in patients with active cancer. Here, we report on the secondary objectives, which were to provide descriptive analyses of clinical characteristics and patterns of use of anticoagulant treatment, and to assess the safety and effectiveness of rivaroxaban in this patient population. Results: Overall, 505 patients were enrolled, and the qualifying venous thromboembolic event was deep vein thrombosis (DVT) only in 45.3% of patients, pulmonary embolism (PE) only in 37.2% of patients, DVT with PE in 9.7% of patients, and catheter-associated DVT in 7.5% of patients (Table). The majority of patients had solid tumors (n=449, 88.9%); 56 patients had hematological malignancies. The most common reasons to switch to rivaroxaban were patient preference/quality of life (n=310, 61.4%) and physician decision (n=174, 34.5%). A total of 150 (29.7%) patients were treated with concomitant chemotherapy and 79 (15.6%) received concomitant radiotherapy. Overall, 117 (23.2%) patients discontinued the study: 59 (11.7%) died, 21 (4.2%) withdrew consent, and 17 (3.4%) were lost to follow-up. 80.2% of patients were treated with rivaroxaban for at least 3 months, and most patients (78.6%) received rivaroxaban 20 mg once daily on study entry. Treatment-emergent adverse events (AEs) were reported: 312 (61.8%) patients had an AE (148 [29.3%] serious AEs), and 95 (18.8%) patients had a bleeding event reported, of which 18 (3.6%) patients had an adjudicated major bleeding event. Adjudicated symptomatic and incidental VTE recurrence occurred in 15 (3.0%) and 3 (0.6%) patients, respectively. Adjudicated other site thromboembolic events such as splanchnic or cerebral vein thromboses were symptomatic in 1 (0.2%) patient and incidental in 1 (0.2%) patient. Conclusions: Observed incidence rates of VTE and bleeding events in COSIMO were similar to previous studies of DOACs for VTE treatment in patients with active cancer (Young AM et al. J Clin Oncol 2018;36:2017; Raskob GE et al. N Engl J Med 2018;378:615). Study governance Bayer AG Funding The COSIMO study is funded by Bayer AG and Janssen Pharmaceuticals. Trial protocol number NCT02742623. Registered 19 April 2016. Documented approval from appropriate independent ethics committees/institutional review boards will be obtained for all participating centers prior to study start. Patients were asked to provide signed informed consent forms before joining the study. Few patients have yet completed the study, and so no data are available to share. Acknowledgements Editorial assistance was provided by Kate Weatherall of Chameleon Communications Int. Ltd. with funding from Bayer AG and Janssen Scientific Affairs, LLC. Disclosures Maraveyas: Bristol-Myers Squibb: Honoraria; Bayer AG: Honoraria, Research Funding; Pfizer: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding. Lee:Pfizer: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Mantovani:Daiichi Sankyo: Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bayer AG: Honoraria; Fondazione Charta: Consultancy; Pfizer: Honoraria. De Sanctis:Bayer US LLC: Employment, Equity Ownership. Abdelgawwad:Bayer AG: Employment. Fatoba:Bayer AG: Employment. Bach:Bayer AG: Employment. Cohen:Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ACI Clinical: Consultancy; CSL Behring: Consultancy; Aspen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ONO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Consultancy, Speakers Bureau; TRN: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Temasek Capital: Consultancy; Boston Scientific: Consultancy; Guidepoint Global: Consultancy; Medscape: Consultancy, Speakers Bureau; McKinsey: Consultancy; Navigant: Consultancy; UK Government Health Select Committee: Other: advised the UK Government Health Select Committee, the all-party working group on thrombosis, the Department of Health, and the NHS, on the prevention of VTE; Leo Pharma: Consultancy; GLG: Consultancy; Johnson and Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

The Real World Experience Regarding the Safety of Rivaroxaban and Apixaban in Venous Thromboembolism Patients with High Bleeding Risk

Background Rivaroxaban and apixaban are two direct oral anticoagulants (DOACs) targeting Factor Xa. Each DOAC was separately proven effective and safe when compared to standard treatment (heparin followed by warfarin) in patients diagnosed with venous thromboembolism (VTE). Several retrospective cohort analyses suggest apixaban may be superior to rivaroxaban due to less bleeding rates. One recent study showed the safety of apixaban and rivaroxaban for acute VTE were comparable. Also, long-term anticoagulation with low molecular weight heparin (LMWH), has never been directly compared with Factor Xa inhibitors. Given the patient population at our facility includes a significant percentage of elderly from nursing homes with multiple comorbidities and significantly higher bleeding risks than the general population, we aimed to evaluate the local real-world DOACs and heparin use with particular focus on safety. Methods A retrospective study was conducted at Kingsbrook Jewish Medical Center. Demographics, relevant laboratory/ imaging studies for patients admitted from 1/2016 to 12/2018 with the diagnosis of VTE based on the ICD 9/10 codes were collected from the IT dept. VTE patients who had bleeding events during the same admission for VTE or were admitted for relevant bleeding events based on ICD 9/10 codes within 6 months from the diagnosis of VTE were identified. Major bleeding events were defined as requiring hospitalization, blood transfusion or a significant drop in hemoglobin (more than 2 g/dl). The rest of the bleeding events were classified as minor. Demographics and clinical characteristics were summarized with means/median for continuous variables and with proportions for categorical variables. The differences in covaries were assessed with chi-square, Fisher exact test or t-tests. Results A total of 177 acute VTE patients were identified in the study. 37.9% (n=67) and 32.8% (n=58) patients were started on rivaroxaban and apixaban, respectively, as monotherapy. 29.3% (n=52) patients were given unfractionated heparin (23%, n=12) or LMWH (77%, n=40) based on the renal function. The bleeding rate in the apixaban group (4/58, 6.9%) was slightly higher than that in the rivaroxaban group (3/67, 4.5%), however, there was no statistical significance. Compared to patients received heparin (11/52, 21.2%), patients started on rivaroxaban (p=0.008) or apixaban (p=0.049) had a significantly lower rate of bleeding. Of note, majority of the bleeding event (16/18) was captured during the same admission when VTE was diagnosed. VTE patients in the apixaban group were older (p = 0.007) and had a longer length of stay (LOS, p= 0.024) compared to the ones in the rivaroxaban group. We then combined rivaroxaban and apixaban into DOAC group. Compared to Heparin group (n=11, 21.1%), the bleeding events in DOAC group (n=7, 5.6%) were significantly less (P=0.0045). Heparin group (n=21, 40.4%) included more patients with cancer than the DOAC group (n=9, 7.2%, p &lt;0.0001), suggesting active malignancy may be correlating with higher bleeding risk. We then looked at the bleeding risk in non-cancer patients. Similarly, we didn't observe any superiority between rivaroxaban (n=2, 3.1%) and apixaban (n=3, 5.8%) regarding bleeding events in non-cancer patients with acute VTE. The average LOS in the apixaban group was significantly longer than that in the rivaroxaban group with non-cancer patients. It may be associated with relatively older age in the apixaban group compared to that in the rivaroxaban group. Most importantly, in patients without active malignancy, we found that the bleeding rate in the DOAC group was only 4.3% while the heparin group had a much high bleeding rate of 16.1% (p=0.035). Discussion Our study suggested that the safety of apixaban and rivaroxaban are comparable in VTE patients. In contrast, heparin including LMWH had much higher bleeding risk compared to either DOAC, especially in the beginning. For patients who are hospitalized for acute VTE, heparin intravenously or subcutaneously are usually initiated while the decision for oral anticoagulants are still pending. However, the benefits of such "bridging with heparin" strategy are not warranted, given the high bleeding risk associated with heparin treatment as shown in our study. Except for hemodynamically instability, excessive burden or clots, or impeding procedures, we recommend that DOACs should be used as monotherapy in VTE patients. Disclosures No relevant conflicts of interest to declare.

Yearly trend of acute venous thromboembolism in patients admitted with heart failure in the United States

ABSTRACTIntroduction: Heart failure (HF) patients are at risk for venous thromboembolism (VTE) during the hospital stay. We aim to study the recent trend of deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE in heart failure patients from years 2000–2013.Methods: We utilized the National (Nationwide) Inpatient Sample database and selected non-pregnant patients over the age of 18 years for this purpose. We selected HF, DVT, PE, and VTE based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). We used STATA for analysis.Results: We noted an increase in prevalence of DVT, PE and composite VTE among HF hospitalizations from 0.55%, 0.17% and 0.76% in 2000 to 0.96%, 0.4% and 1.46%, respectively, in 2013 and a decrease in trend of mortality among HF hospitalizations associated with DVT, PE and VTE from 8.95%, 16.36% and 10.80% in 2000 to 6.78%, 7.92% and 7.20%, respectively, in 2013.Conclusion: Increasing prevalence of VTE is concerning and suggests that we still need to work on delivering prophylaxis to all HF inpatients.

Utility of a Nurse-Led Pathway for Patients with Acute Venous Thromboembolism Discharged on Rivaroxaban: A Prospective Cohort Study.

The highest risk of adverse events for patients with acute venous thromboembolism (VTE) is during the early anticoagulation period. However, no established model exists for early clinical monitoring of patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). The authors' aim was to evaluate the utility of a nurse-led pathway to minimize adverse events in acute VTE patients starting on rivaroxaban. The rivaroxaban VTE treatment pathway is a prospective cohort study of consecutive patients with objectively confirmed VTE between July 2015 and May 2017. Primary outcome was the proportion of patients identified at major risk of adverse events (bleeding or recurrent VTE). Secondary outcomes were rates of interventions, major or clinically relevant nonmajor bleeding (CRNMB), recurrent VTE, and all-cause mortality at 90 days. Among 304 participants, 5% (n = 15) were identified to be at major and 9% (n = 28) at possible risk for adverse events. Appropriate interventions to prevent harm were required in 40 patients. Rates of major bleeding, CRNMB, recurrence, and all-cause mortality were 0.3% (95% confidence interval [CI]: 0.1-1.8), 7.2% (95% CI: 4.8-10.7), 1.0 (95% CI: 0.3-2.9), and 1.6% (95% CI: 0.7-3.8), respectively. In conclusion, following discharge of acute VTE patients, a nurse-led pathway identified one in seven (14%) patients at major or possible risk of adverse events. Preemptive interventions to reduce harm translated into the low rates of bleeding and recurrence. The authors' experience highlights the feasibility and importance of a structured clinical surveillance pathway for acute VTE patients initiating NOAC therapy.

The impact of co-morbidity on the disease burden of VTE.

Venous thromboembolism (VTE) is often accompanied by co-morbidities, which complicate and confound data interpretation concerning VTE-related mortality, costs and quality of life. We aimed to assess the contribution of co-morbidities to the burden of VTE. The PREFER in VTE registry, across seven European countries, documented and followed acute VTE patients over 12 months. Patients with co-morbidities were grouped in major co-morbidity groups: cancer, cardiovascular (CV) comorbidity (other than VTE), CV risks, venous, renal, liver, respiratory, bone and joint diseases, and lower extremity paralysis. Mortality rates and health-related quality of life (HrQoL) utility values grouped per co-morbidity were compared to the UK general population. Regression analyses were performed to determine the impact of co-morbidities on mortality and HrQoL. VTE were analyzed together and separately as pulmonary embolism (PE) and deep vein thrombosis (DVT). In total, 3455 patients were included, 40.5% with PE and 59.5% with DVT. 13% and 16% of the PE and DVT patients had no co-morbidities and had a 12-month mortality rate of 1.8% and 1.7%, respectively. Frequency and severity of co-morbidities increased mortality rates up to 30%. The EQ-5D-5L index in patients without co-morbidities were 0.826 and 0.838 for PE and DVT. These scores decreased to 0.638 and 0.555 in the presence of co-morbidities. Co-morbidities in VTE patients are common. VTE had an impact on mortality and HrQoL, and additional impact of co-morbidities was seen. Awareness of the presence of co-morbidities is important when making VTE-related treatment decisions. The presence of co-morbidities in PE and DVT patients is common and their frequency and severity in VTE patients have a substantial impact on mortality rates and HrQoL. When adjusting for co-morbidities, the impact of VTE on mortality as well as health-related quality of life remains present. Assessing patients without consideration of co-morbidities might lead to misinterpretations of the disease burden of PE and DVT.