Tinzaparin and VKA use in patients with cancer associated venous thromboembolism: A retrospective cohort study

International audienceNTRODUCTION:After 6months, little is known about the optimal anticoagulant strategy for an acute episode of VTE in cancer patients.AIMS, OBJECTIVES AND METHODS:The objective was to determine the risk of recurrent VTE and anticoagulant-related bleeding at 6months of follow-up and after 6months, in cancer patients who received tinzaparin during at least 3months for an acute episode of VTE. We conducted a multicenter retrospective cohort study from January 2004 to March 2011.RESULTS:Two hundred fifty patients were included. Stopping anticoagulation before 6months in patients considered at low risk by physicians (i.e.; patients who had prior cancer surgery) and for another reason than bleeding or death was the only factor associated with a significant increased risk of recurrent VTE (OR 7.2 95%CI, 2.0-25.7; p=0.002). The type of anticoagulation did not influence the risk of recurrent VTE. We found a trend towards an increased risk of recurrent VTE when anticoagulation was stopped because of major bleeding while on anticoagulant therapy and patients with metastatic cancer (OR 2.3, 95%CI, 0.9-5.4; p=0.07; and OR 1.8 95%CI, 1.0-3.3; p=0.07; respectively). No factors were found to increase the risk of major bleeding at 6months and after. The overall mortality was 42.8%.CONCLUSIONS:The risk of recurrent VTE was mainly related to early discontinuation of anticoagulation in patients considered at low risk of recurrence (after surgery). When the anticoagulation was stopped before the sixth month, the risk was eight fold higher. After 6month, the risks of recurrent VTE, major bleeding and death were similar in patients with either VKA or tinzaparin when patients were treated according to the guidelines

Site of venous thromboembolism and prothrombotic mutations according to body mass index. Results from the EDITH study.

International audienceThis study evaluated the impact of body mass index (BMI) on venous thromboembolism (VTE) site and assessed a possible interaction between BMI and prothrombotic risk factors in patients included in the EDITH (Etude des Déterminants et Interactions de le THrombose veineuse) study. A cross-sectional study was used to compare the site of unprovoked VTE according to BMI categories in 1077 patients and a matched case-control study (732 pairs) assessed the joint effect of BMI and prothrombotic mutations on VTE risk. The cross sectional analysis showed that the proportion of patients with pulmonary embolism was higher in overweight (63%) and obese (63*5%) patients than among patients with a BMI<25kg/m(2) (55%), P=0*02 and P=0*05 respectively. No interaction was found between F5 G1691A (factor V Leiden) and BMI for VTE risk (P=0*90). There was a significant interaction between F2 G20210A and BMI (P=0*02). The risk of VTE associated with BMI was 1*7 [95% confidence interval (CI): 0*8-3*7], 4*36 (95%CI: 1*49-12*78) and 12*03 (95%CI: 1*53-94*29) in patients with BMI<25kg/m(2) , 25≤BMI<30 and ≥30kg/m(2) respectively after adjustment for age and oestrogen use. This study showed that BMI may play a role in determining the site of VTE and may interact with F2 G20210A but not with F5 G1691A for the risk of VTE

Comparison of standard prophylactic, intermediate prophylactic and therapeutic anticoagulation in patients with severe COVID-19: protocol for the ANTICOVID multicentre, parallel-group, open-label, randomised controlled trial

International audienceIntroduction COVID-19 induces venous, arterial and microvascular thrombosis, involving several pathophysiological processes. In patients with severe COVID-19 without macrovascular thrombosis, escalating into high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) could be beneficial in limiting the extension of microvascular thrombosis and forestalling the evolution of lung and multiorgan microcirculatory dysfunction. In the absence of data from randomised trials, clinical practice varies widely. Methods and analysis This is a French multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three anticoagulation strategies in patients with COVID-19. Patients with oxygen-treated COVID-19 showing no pulmonary artery thrombosis on computed tomography with pulmonary angiogram will be randomised to receive either low-dose PA, HD-PA or TA for 14 days. Patients attaining the extremes of weight and those with severe renal failure will not be included. We will recruit 353 patients. Patients will be randomised on a 1:1:1 basis, and stratified by centre, use of invasive mechanical ventilation, D-dimer levels and body mass index. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality, followed by the time to clinical improvement defined as the time from randomisation to an improvement of at least two points on the ordinal clinical scale. Secondary outcomes include thrombotic and major bleeding events at day 28, individual components of the primary endpoint, number of oxygen-free, ventilator-free and vasopressor-free days at day 28, D-dimer and sepsis-induced coagulopathy score at day 7, intensive care unit and hospital stay at day 28 and day 90, and all-cause death and quality of life at day 90. Ethics and dissemination The study has been approved by an ethical committee (Ethics Committee, Ile de France VII, Paris, France; reference 2020-A03531-38). Patients will be included after obtaining their signed informed consent. The results will be submitted for publication in peer-reviewed journals. Trial registration number NCT04808882

COVID-19 in Patients with Pulmonary Hypertension A National Prospective Cohort Study

RATIONALE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. OBJECTIVES: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. METHODS: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. MEASUREMENTS AND MAIN RESULTS: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients (n = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P, 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. CONCLUSIONS: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population

COVID-19 in Patients with Pulmonary Hypertension: A National Prospective Cohort Study

International audienceRationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients (n = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study

International audienceBackground: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France.Methods: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease.Results: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]).Conclusion: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19