Cancer-associated thrombosis (CAT) is a frequent and severe complication of malignancy. While patients are anticoagulated, risks of recurrent venous thromboembolism (VTE) and major bleeding (MB) remain substantial, but data are limited according to specific tumor sites and in patients with frailty. Our objective was to evaluate 6-month incidences of recurrent VTE, MB, and death in patients with CAT treated with tinzaparin, and to assess the influence of tumor site and frailty on these risks. Individual patient-level data from 1,413 patients were pooled from three prospective cohort studies and the tinzaparin arm of a randomized controlled trial. Frailty was defined as age ≥75 years, creatinine clearance <50 mL/min, body weight ≤50 kg, or ECOG ≥2. Cumulative incidences were estimated using Kalbfleisch and Prentice method and plotted to illustrate the benefit-risk balance by tumor site and frailty. At 6 months, cumulative incidences of recurrent VTE and MB were 6.2% and 3.4%, respectively. Recurrent VTE incidence surpassed MB incidence in gastrointestinal, lung, genitourinary, and gynecological cancers, whereas MB risk exceeded VTE risk in breast cancer. Among patients with frailty criteria, recurrent VTE risk increased with the number of frailty factors, while MB remained relatively stable. In patients with CAT receiving tinzaparin, VTE recurrence, unlike bleeding risk, varies according to tumor site and patient frailty.. In CAT patients with frailty treated with standard full-dose tinzaparin, these findings do not support routine dose modification.

BACKGROUND:In patients with active cancer and venous thromboembolism, whether extended treatment with a reduced dose of an oral anticoagulant is effective in preventing recurrent thromboembolic events and decreasing bleeding is unclear. METHODS:We conducted a randomized, double-blind, noninferiority trial with blinded central outcome adjudication. Consecutive patients with active cancer and proximal deep-vein thrombosis or pulmonary embolism who had completed at least 6 months of anticoagulant therapy were randomly assigned in a 1:1 ratio to receive oral apixaban at a reduced (2.5 mg) or full (5.0 mg) dose twice daily for 12 months. The primary outcome was centrally adjudicated fatal or nonfatal recurrent venous thromboembolism, assessed in a noninferiority analysis (margin of 2.00 for the upper boundary of the 95% confidence interval of the subhazard ratio). The key secondary outcome was clinically relevant bleeding, assessed in a superiority analysis. RESULTS:A total of 1766 patients underwent randomization at a median time since the index event of 8.0 months (interquartile range, 6.5 to 12.6); 866 patients were assigned to the reduced-dose group, and 900 to the full-dose group. The median treatment duration was 11.8 months (interquartile range, 8.3 to 12.1). Recurrent venous thromboembolism occurred in 18 patients (cumulative incidence, 2.1%) in the reduced-dose group and in 24 (cumulative incidence, 2.8%) in the full-dose group (adjusted subhazard ratio, 0.76; 95% confidence interval [CI], 0.41 to 1.41; P = 0.001 for noninferiority). Clinically relevant bleeding occurred in 102 patients (cumulative incidence, 12.1%) in the reduced-dose group and in 136 (cumulative incidence, 15.6%) in the full-dose group (adjusted subhazard ratio, 0.75; 95% CI, 0.58 to 0.97; P = 0.03). Mortality was 17.7% in the reduced-dose group and 19.6% in the full-dose group (adjusted hazard ratio, 0.96; 95% CI, 0.86 to 1.06). CONCLUSIONS:Extended anticoagulation with reduced-dose apixaban was noninferior to full-dose apixaban for the prevention of recurrent venous thromboembolism in patients with active cancer. The reduced dose led to a lower incidence of clinically relevant bleeding complications than the full dose. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; API-CAT ClinicalTrials.gov number, NCT03692065.).

Background:Risk of venous thromboembolism (VTE) recurrence remains high in patients with cancer-associated thrombosis (CAT), despite therapeutic anticoagulation. Identifying patients at risk of treatment failure is still a challenge. Objectives:We aimed to assess the performance of the Ottawa score in predicting VTE recurrence in a large homogeneous population of patients with CAT treated with the same anticoagulant, tinzaparin, for at least 3 months. Methods:Individual patient data from 3 prospective cohort studies and 1 randomized controlled trial were pooled (PROSPERO: CRD42019119907). Clinical events of interest were adjudicated by independent central adjudication committees in all 4 studies. Results:Among the 1413 patients included, the Ottawa score could be calculated for 1088 of whom 646 (59.4%) were classified at high risk of recurrence (Ottawa score ≥ 1). The 6-month cumulative incidence of recurrent VTE was 5.0% (95% CI, 3.2-7.8) in the Ottawa low-risk group and 8.5% (95% CI, 6.6-10.8) in the high-risk group. The area under the receiver operating characteristic curve was 0.56 (95% CI, 0.51-0.62). The sensitivity of the dichotomized Ottawa score (score ≥ 1) was 72.8% (95% CI, 62.6%-83.0%), the specificity was 41.9% (95% CI, 37.8%-45.9%), the positive predictive value was 8.6% (95% CI, 6.4%-10.8%), and the negative predictive value was 95.3% (95% CI, 93.3%-97.4%). Introducing additional predictive factors failed to significantly improve the score's performance. Conclusions:Despite the large number of patients and anticoagulant treatment standardization, the Ottawa score failed to accurately predict recurrent VTE in patients with CAT treated with tinzaparin.

Background: Biomarkers to identify lung cancer (LC) patients with high risk of venous thromboembolism (VTE) are needed. Objectives: To evaluate the usefulness of plasma tissue factor activity (TFA) and D-dimer levels for the prediction of VTE and overall survival in patients with LC. Methods: In a prospective multicenter observational cohort of consecutive LC patients, TFA and D-dimer levels were measured at diagnosis before any cancer treatment (V1) and between 8 and 12 weeks after diagnosis (V2) Results: Among 302 patients, 38 (12.6%) experienced VTE within the first year after diagnosis. V1-TFA and V1-D-dimer levels were significantly (P = .02) higher in patients who presented VTE within 3 months than in patients without VTE: V1-TFA was 2.02 (25th-75th percentiles, 0.20-4.01) vs 0.49 (0.20-3.09) ng/mL and V1-D-dimer was 1.42 (0.64-4.40) vs 0.69 (0.39-1.53) mu g/mL, respectively. Cutoffs of 1.92 ng/mL for TFA and 1.26 mu g/mL for D-dimer could discriminate both groups of patients. In multivariate analysis, V1-TFA > 1.92 ng/mL was the only significant predictor of VTE risk at 1 year (hazard ratio, 2.10; 95% CI, 1.06-4.16; P = .03). V2-TFA, quantified in 251 patients, decreased significantly compared with V1-TFA (0.20 vs 0.56 ng/mL, P < .05), but a V2TFA level > 0.77 ng/mL could predict VTE in the following 3 months. Median overall survival was worse for patients with V1-TFA > 1.92 ng/mL (14.6 vs 23.8 months) and V1-D-dimer > 1.26 mu g/mL (13.8 vs 24 months, P < .001). Conclusion: High plasma TFA levels are associated with the occurrence of VTE within the next 3 months after each visit (V1 or V2) and poor survival.

Cancer-associated thrombosis (CAT) is a common complication during cancer, with complex management due to an increased risk of both recurrence and bleeding. Bevacizumab is an effective anti-angiogenic treatment but increases the risk of bleeding and potentially the risk of venous thromboembolism (VTE). The aim of this study was to evaluate the efficacy and safety of anticoagulant therapy in patients with CAT receiving bevacizumab, according to the continuation or discontinuation of bevacizumab. In a retrospective multicenter study, patients receiving anticoagulant for CAT occurring under bevacizumab therapy were included. The primary endpoint combined recurrent VTE and/or major or clinically relevant non-major bleeding. Among the 162 patients included, bevacizumab was discontinued in 70 (43.2%) patients and continued in 92 (56.8%) patients. After a median follow-up of 318 days, 21 (30.0%) patients in the discontinuation group experienced VTE recurrence or major or clinically relevant non-major bleeding, compared to 27 (29.3%) in the continuation group. The analysis of survival following the first event showed no significant difference between the groups in uni- or multivariate analysis (p = 0.19). The primary endpoint was not influenced by the duration of bevacizumab exposure. These results suggest that the efficacy and safety of anticoagulant therapy in patients with CAT receiving bevacizumab is not modified regardless of whether bevacizumab is continued or discontinued.

Introduction DOAC (direct oral anticoagulant) and LMWH (Low Molecular Weight Heparin) are recommended by international guidelines as first line therapy in patients with CAT (Cancer Associated Thrombosis), but the risk of venous thromboembolic recurrence (rVTE) and the risk of major bleeding (MB) remains high. Several scores have attempted to predict these risks with disappointing results, probably because of heterogeneous treatments and small sample sizes representing various tumor sites. We conduct a meta-analysis on individual patient level data to report the rate of rVTE and MB by 6 months according to site of cancer from prospective studies involving CAT patients on tinzaparin. Methods The meta-analysis is based on individual patient data from prospective studies that included patients with CAT treated with tinzaparin who were followed for 6 months (PROSPERO registration CRD42019119907). Eligible studies must include controlled data and a central decision for study outcomes. Main outcomes were cumulative incidence of rVTE and MB at 6 months. Time-to-event outcomes were estimated using competing risk regression (Fine and Gray's method with death as competing risk). Cumulative incidences were presented with corresponding 95% confidence interval (95% CI). Time-to-event outcomes were estimated using competing risk regression (Fine and Gray's method with death as competing risk). Cumulative incidences were presented with corresponding 95% confidence interval (95% CI). Results Three prospective cohort studies (AXA - NCT02898051, 308 patients; PREDICARE - NCT03099031, 409 patients (1); TICAT - NCT01164046, 247 patients (2) and the Tinzaparin arm of the CATCH study (NCT01130025, 449 patients (3)) were included. A total of 1413 patients (median age 65.0 [IQR 56.0-73.5], 51.9% female) were included in the meta-analysis. Cancers were mostly solid tumors (91.7%); primary sites were gastrointestinal (27.0%), lung (18.0%), breast (11.8%), genitourinary (14.4%); ECOG performance status was ≥ 2 for 30.2%. At 6 months, 74 patients experienced a rVTE, for a cumulative incidence of 5.4% [95% CI: 4.3%; 6.7%], while 47 patients had a MB, for a cumulative incidence of 3.4% [95% CI: 2.6%; 4.6%]. Clinical outcomes according to the type of cancer are summarized in the Table. rVTE cumulative incidence varied from 0.6 to 8.5% and rVTE occurred more frequently in patients with genitourinary, lung and gynecological cancers, while MB cumulative incidence ranged from 2.1% to 4.2% across different cancer sites (Table). Overall mortality ranged from less than 18% (breast and hematological cancers) to 45.2% (lung cancer) within 6 months of the index VTE. Conclusion In CAT patients receiving tinzaparin for up to 6 months, rVTE and MB vary according to tumor site. The CAT entity is not sufficient to describe a situation at risk of recurrence or bleeding for patient management. References 1.Jara-Palomares L et al. Tinzaparin in cancer associated thrombosis beyond 6months: TiCAT study. Thromb Res. 2017; 157:90-96. 2. Girard P, et al. Failure of the Ottawa Score to Predict the Risk of Recurrent Venous Thromboembolism in Cancer Patients: The Prospective PREDICARE Cohort Study. Thromb Haemost. 2022; 122:151-157. 3. Lee AYY et al. CATCH Investigators. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. JAMA. 2015; 314(7):677-686.

Background: In recent years, knowledge about cancer associated thrombosis has evolved considerably. Methods: Practical guidelines were drafted on the initiative of the INNOVTE FCRIN Network, led by the French Speaking Society of Respiratory Diseases (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of different scientific societies practicing in various settings. The method fol-lowed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS). Results: After a literature review, guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease and management from the data of avail-able clinical trials and observational studies : epidemiology, initial treatment, treatment duration, extended treatment, recurrent thrombosis, central venous catheter thrombosis, incidental thrombosis, treatment in case of thrombocytopenia. Conclusion: These evidence-based guidelines are intended to guide the practical management of patients with cancer associated thrombosis (c) 2023 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

BACKGROUND: Admission to the hospital is a major risk factor for the development of venous thromboembolism (VTE). Whether thromboprophylaxis with low-molecular-weight heparin prevents symptomatic VTE in medically ill, hospitalized older adults remains debated. METHODS: In a prospective, randomized, placebo-controlled, double-blind, multicenter trial, older adults (>70 years of age) hospitalized for acute medical conditions were randomly assigned to receive 40 mg a day of low-molecular-weight heparin (enoxaparin) or placebo for 6 to 14 days. The primary efficacy outcome was the cumulative incidence of symptomatic VTE (distal or proximal deep vein thrombosis, fatal or nonfatal pulmonary embolism) at 30 days. The primary safety outcome was major bleeding. Secondary outcomes included efficacy and safety outcomes at 90 days. RESULTS: The trial was prematurely discontinued in September 2020, 5 years after enrollment began, because of drug supply issues. By the time of trial discontinuation, 2559 patients had been randomly assigned at 47 centers. Median age was 82 years and 60% of patients were female. In the intention-to-treat population, the primary efficacy outcome occurred in 22 out of 1278 (cumulative incidence, 1.8%) patients in the enoxaparin group and in 27 out of 1263 (cumulative incidence, 2.2%) patients in the placebo group (cumulative incidence difference, −0.4 percentage points; 95% confidence interval, −1.5 to 0.7), with no significant difference in time to VTE (P=0.46). The incidence of major bleeding was 0.9% in the enoxaparin group and 1.0% in the placebo group. At 90 days there were 14 symptomatic pulmonary emboli in the enoxaparin group and 25 in the placebo group; all 39 pulmonary embolism events resulted in hospital readmission and/or death, with 5 deaths from pulmonary embolism in the enoxaparin group and 11 deaths in the placebo group. CONCLUSIONS: This trial of thromboprophylaxis in medically ill, hospitalized older adults did not demonstrate that enoxaparin reduced the risk of symptomatic VTE after 1 month. Because the trial was prematurely discontinued, larger trials are needed to definitively address this question. (Funded by the French Ministry of Health Programme Hospitalier de Recherche Clinique, grant number PHRC-N-13-0283; ClinicalTrials.gov number, NCT02379806.)

Background: The prevalence of pulmonary embolism (PE) is approximately 11-17 % in patients with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The optimal diagnostic strategy for PE in these patients remains undetermined. Aims: To evaluate the safety and efficacy of standard (revised Geneva and Wells PE scores combined with fixed D-dimer cut-off) and computed tomography pulmonary angiogram (CTPA)-sparing diagnostic strategies (ADJUST-PE, YEARS, PEGeD, 4PEPS) in patients with AE-COPD.Method: Post-hoc analyses of data from the multicenter prospective PEP study were performed. The primary outcome was the diagnostic failure rate of venous thromboembolism (VTE) during the entire study period. Secondary outcomes included diagnostic failure rate of PE and deep venous thrombosis (DVT), respectively, during the entire study period and the number of CTPA needed per diagnostic strategy.Results: 740 patients were included. The revised Geneva and Wells PE scores combined with fixed D-dimer cut-off had a diagnostic failure rate of VTE of 0.7 % (95%CI 0.3 %-1.7 %), but >70.0 % of the patients needed imaging. All CTPA-sparing diagnostic algorithms reduced the need for CTPAs (-10.1 % to-32.4 %, depending on the algorithm), at the cost of an increased VTE diagnosis failure rate of up to 2.1 % (95%CI 1.2 %-3.4 %).Conclusion: Revised Geneva and Wells PE scores combined with fixed D-dimer cut-off were safe, but a high number of CTPA remained needed. CTPA-sparing algorithms would reduce imaging, at the cost of an increased

Objectives Chatbots, conversational agents that walk medical students (MS) though a clinical case, are serious games that seem to be appreciated by MS. Their impact on MS’s performance in exams however was not yet evaluated. Chatprogress is a chatbot-based game developed at Paris Descartes University. It contains 8 pulmonology cases with step-by-step answers delivered with pedagogical comments. The CHATPROGRESS study aimed to evaluate the impact of Chatprogress on students’ success rate in their end-term exams. Methods We conducted a post-test randomized controlled trial held on all fourth-year MS at Paris Descartes University. All MS were asked to follow the University’s regular lectures, and half of them were randomly given access to Chatprogress. At the end of the term, medical students were evaluated on pulmonology, cardiology and critical care medicine. Main outcomes measures The primary aim was to evaluate an increase in scores in the pulmonology sub-test for students who had access to Chatprogress, compared to those who didn’t. Secondary aims were to evaluate an increase in scores in the overall test (Pulmonology, Cardiology and Critical care medicine test (PCC)) and to evaluate the correlation between access to Chatprogress and overall test score. Finally, students’ satisfaction was assessed using a survey. Results From 10/2018 to 06/2019, 171 students had access to Chatprogress (the Gamers) and among them, 104 ended up using it (the Users). Gamers and Users were compared to 255 Controls with no access to Chatprogress. Differences in scores on the pulmonology sub-test over the academic year were significantly higher among Gamers and Users vs Controls (mean score: 12.7/20 vs 12.0/20, p = 0.0104 and mean score: 12.7/20 vs 12.0/20, p = 0.0365 respectively). This significant difference was present as well in the overall PCC test scores: (mean score: 12.5/20 vs 12.1/20, p = 0.0285 and 12.6/20 vs 12.1/20, p = 0.0355 respectively). Although no significant correlation was found between the pulmonology sub-test’s scores and MS’s assiduity parameters (number of finished games among the 8 proposed to Users and number of times a User finished a game), there was a trend to a better correlation when users were evaluated on a subject covered by Chatprogress. MS were also found to be fans of this teaching tool, asking for more pedagogical comments even when they got the questions right. Conclusion This randomised controlled trial is the first to demonstrate a significant improvement in students’ results (in both the pulmonology subtest and the overall PCC exam) when they had access to Chatbots, and even more so when they actually used it.

Introduction Venous thromboembolism (VTE) is a difficult to treat condition in patients with cancer with a persisting risk of recurrent VTE during anticoagulant treatment with low-molecular weight heparin (LMWH). Recent data suggest that direct oral anticoagulants (DOACS) are associated with a lower risk of recurrence but a higher risk of bleeding in these patients. Predicting the risk of recurrent VTE with LMWH may help to select the best treatment option. We conducted a prospective multicenter observational cohort study in cancer patients with VTE treated with tinzaparin for 6 months in order to validate the Ottawa score (NCT03099031) and search for additional risk of recurrent VTE. The Ottawa score is composed of 5 variables, female sex (+1), lung cancer (+1), breast cancer (-1) cancer stage 1 (-2) and previous DVT (+1). A score ≤0 is associated with a low risk of recurrent VTE. Methods Adult cancer patients with recent diagnosis of documented symptomatic or incidental VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE) treated with tinzaparin for 6 months were included in the study. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment with tinzaparin. Other endpoints were symptomatic recurrent VTE, major bleeding, heparin induced thrombocytopenia (HIT), all-cause mortality within 3 and 6 months. All events were adjudicated by a Central Adjudication Committee. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. Cumulative incidences were presented with corresponding 95% confidence interval (95% CI). To validate the Ottawa score, the area under the curve (AUC) and its 95% CI were calculated on receiver operating characteristic (ROC) curve analysis; the most discriminant cut-off was then determined by calculating the Youden index. Univariate and multivariate analyses were performed to identify additional predictive factors of recurrent VTE to those included in the Ottawa score using the Fine and Gray method and adjusted on factors included in the Ottawa score. Hazard ratio and their 95% CI were calculated. Results A total of 409 patients were included and analyzed on an intention-to-treat basis; the median age was 68 years and 51% of patients were males. 60.4% of patients had a PE (with or without DVT) .64% received chemotherapy at inclusion or in the month before inclusion. Lung (31.3%) and digestive track (18.3%) cancers were the most common cancer types and 67.0% had stage IV cancers. According to Ottawa score, 58% of patients were classified at high clinical probability of recurrence (score ≥ 1). During the 6 months treatment period, 23 patients had a recurrent VTE, yielding a cumulative incidence of 6.1% (95% CI 4.0-9.3) with a median time for recurrent VTE of 33 days. The recurrence rate of VTE was estimated to 7.8% (95% CI 4.9-12.5) for patients classified at high risk of recurrence according to the Ottawa score (score ≥ 1) compared to 3.8% (95%CI 1.6-8.9) for other patients (Ottawa score < 1). AUC of the Ottawa score was 0.60 (95% CI 0.55-0.65). In multivariable analysis, none of the potential risk factors for recurrent VTE was significantly associated with recurrent VTE at 6 months. During the 6 months treatment period, 15 patients had a major bleeding and 2 patients experienced a HIT. At 3 and 6 months, 104 and 144 patients had died yielding a cumulative incidence of 26.1%, (95% CI 21.8-30.4) and 37.8% (95% CI 32.8-42.9), respectively. The main cause of death was underlying cancer. Conclusion In this prospective cohort of patients with cancer receiving LMWH for VTE, the Ottawa score did not accurately predict recurrent VTE. No other clinical predictor of recurrent VTE was identified in this study. Disclosures Meyer: Bayer: Other: travel support; LEO pharma: Other: travel support, Research Funding; SANOFI: Other: travel support, Research Funding; BMS-Pfizer: Other: travel support, Research Funding; Boehringer Ingelheim: Research Funding. Girard:Leo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Scotté:LEO Pharma A/S: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Tesaro: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau; MSD: Honoraria, Research Funding, Speakers Bureau; Pierre Fabre Oncology: Honoraria, Research Funding, Speakers Bureau. Lamblin:Leo Pharma: Employment. Laporte:Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boston scientific: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Leo-Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees.

This consensus document is proposed to clinicians to provide the whole spectrum of deep vein thrombosis management as an update to the 2017 consensus document. New data guiding clinicians in indicating extended anticoagulation, management of patients with cancer, and prevention and management of post-thrombotic syndrome are presented. More data on benefit and safety of non-vitamin K antagonists oral anticoagulants are highlighted, along with the arrival of new antidotes for severe bleeding management.

This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control.

AIMS:The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment.METHODS AND RESULTS:Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm.CONCLUSIONS:For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications.

IMPORTANCE:The prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain.OBJECTIVE:To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms.DESIGN, SETTING, AND PARTICIPANTS:Multicenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017.EXPOSURES:Acutely worsening respiratory symptoms in patients with COPD.MAIN OUTCOMES AND MEASURES:The primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not.RESULTS:Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P < .001). The prevalence of venous thromboembolism was 11.7% (95% CI, 8.6%-15.9%) among patients in whom pulmonary embolism was suspected (n = 299) and was 4.3% (95% CI, 2.8%-6.6%) among those in whom pulmonary embolism was not suspected (n = 441).CONCLUSIONS AND RELEVANCE:Among patients with chronic obstructive pulmonary disease admitted to the hospital with an acute worsening of respiratory symptoms, pulmonary embolism was detected in 5.9% of patients using a predefined diagnostic algorithm. Further research is needed to understand the possible role of systematic screening for pulmonary embolism in this patient population.

parameters. 9,10 Accordingly, patients are classi fi ed into the intermediate – high-risk category if they have evidence of right ventricular (RV) dysfunction on echocardiography or computed tomography pulmonary angiography, in combination with elevated plasma cardiac troponin levels. Abstract Intermediate – high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion ef fi cacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identi fi er: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the ef fi cacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate – high-risk PE will also ful fi ll at least one clinical criterion of severity: systolic blood pressure (cid:1) 110 mm Hg, respiratory rate > 20 breaths/min, or history of heart failure. The primary ef fi cacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical bene fi t (primary ef fi cacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limita-tion, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations. in future state-of-the-art randomized controlled trials. the results the present trial expected a major impact on future risk-adjusted treatment strategies for patients with acute

INTRODUCTION:Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Previous studies reported pulmonary embolism (PE) in severe COVID-19 patients. Aim of the study was to estimate the prevalence of symptomatic PE in COVID-19 patients and to identify the clinical, radiological or biological characteristics associated with PE.PATIENTS/METHODS:We conducted a retrospective nested case-control study in 2 French hospitals. Controls were matched in a 1:2 ratio on the basis of age, sex and center. PE patients with COVID-19 were compared to patients in whom PE was ruled out (CTPA controls) and in whom PE has not been investigated (CT controls).RESULTS:PE was suspected in 269 patients among 1042 COVID-19 patients, and confirmed in 59 patients (5.6%). Half of PE was diagnosed at COVID-19 diagnosis. PE patients did not differ from CT and CTPA controls for thrombosis risk factors. PE patients more often required invasive ventilation compared to CTPA controls (odds ratio (OR) 2.79; 95% confidence interval (CI) 1.33-5.84) and to CT controls (OR 8.07; 95% CI 2.70-23.82). PE patients exhibited more extensive parenchymal lesions (>50%) than CT controls (OR 3.90; 95% CI 1.54-9.94). D-dimer levels were 5.1 (95% CI 1.90-13.76) times higher in PE patients than CTPA controls.CONCLUSIONS:Our results suggest a PE prevalence in COVID-19 patients close to 5% in the whole population and to 20% of the clinically suspected population. PE seems to be associated with more extensive lung damage and to require more frequently invasive ventilation.

BackgroundCurrent guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe.MethodsWe did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555).FindingsBetween Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0–78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210–224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1–5]) of 402 patients had at least one major bleeding event and 16 (4% [2–6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran.InterpretationA strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation.FundingGerman Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim.

8532 Background: Venous thromboembolism (VTE) is associated with tumor aggressiveness and mortality in cancers. Tissue Factor is the main activator of the coagulation but its variations in lung cancers (LC) have been less studied than D-dimers (DDi). We assessed plasma Tissue Factor Activity (TFa) and DDi and VTE events and mortality in patients with LC. Methods: This prospective study included patients, from 5 hospitals, recently diagnosed LC, without prior VTE or anticoagulant therapy within the last 2 months. Clinical and tumor data, Khorana score (KS), VTE events and overall survival (OS) were assessed (follow up 2 years). Blood samples were collected before any cancer treatment (V1): DDi (HemosIL) and TFa (chromogenic assay, Diagnostica Stago) were analyzed in a central lab. Independent nonparametric tests were used for group comparisons. A relevant clinical threshold of both markers was determined :1500 μg/ml for DDi and 1.2 ng/ml for TFa. Early death was compared using Cox model and Kaplan Meier curves and logrank tests. All tests were two-tailed tests and 0.05 was considered as significant. Results: Between 12/2014 and 01/2017, 302 consecutive patients (pts) were included (mean age 64 years, 61% males, 89% smokers, 85% NSCLC, 67% stage IV). At V1, TFa levels increased with cancer stage (p = 0.004) but not DDi. VTE incidence was 13,9%: 39 events (62% incidental and 51% pulmonary embolism) with 33 events within 6 months. KS failed to predict VTE (KS > 3 in 23% of the pts in VTE group vs 21% of the 302 pts, p = 0.42). DDi and TFa levels were not significantly different in VTE pts than in no VTE pts. But, a TFa > 1.2 ng/ml was significantly predictive in occurrence of VTE within the first 6 months (57.6% of the VTE pts vs 38.8% of no VTE pts, p = 0.04), and also within the first year (p = 0.03). Median OS was 17,6 months (m) in VTE pts and 19.5 m in no VTE pts (p = 0,97). Compared to survivors, higher levels of DDi and TFa were observed for the 38 pts who died within 6 months : 1.82 vs 0.67 μg/ml (p < 0.001) and 1.95 vs 0.33 ng/ml (p < 0.001) respectively. These differences were observed for the 97 pts who died during the first year, too. With thresholds of TFa > 1.2 ng/ml and DDi > 1500 μg/ml, median OS was significantly shorter: 14.4 m vs > 29.8 m ( p < 0,001) and 13.8 m vs 22.6 m (p < 0.001), respectively. Conclusions: High TFa level discriminates a population with high risk to VTE and early death in LC. This biomarker could take place in a predictive score. Clinical trial information: NCT02853188.