Inhibition of Factor XI: A New Era in the Treatment of Venous Thromboembolism in Cancer Patients?

Direct oral anticoagulants against activated factor X and thrombin were the last milestone in thrombosis treatment. Step by step, they replaced antivitamin K and heparins in most of their therapeutic indications. As effective as the previous anticoagulant, the decreased but persistent risk of bleeding while using direct oral anticoagulants has created space for new therapeutics aiming to provide the same efficacy with better safety.

Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial.

Background: Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients.

Methods: In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

Background: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs.

Methods: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology.

Pulmonary Embolism in the Cancer Associated Thrombosis Landscape.

In cancer patients, pulmonary embolism (PE) is the second leading cause of death after the cancer itself, most likely because of difficulties in diagnosing the disease due to its nonclassical presentation. The risk of PE recurrence and possibly the case-fatality rate depends on whether the patient presents a symptomatic PE, an unsuspected PE, a subsegmental PE, or a catheter-related PE. Choosing the best therapeutic option is challenging and should consider the risk of both the recurrence of thrombosis and the occurrence of bleeding.

Management of acute venous thromboembolism in patients taking antiplatelet therapy.

Background: Concomitant anticoagulant and antiplatelet therapy increases bleeding risk, but most data are derived from patients with atrial fibrillation. Patients with venous thromboembolism (VTE) may differ.

Objective: To study the management of patients diagnosed with acute VTE while receiving antiplatelet treatment.

Implementation of a systematic comprehensive geriatric assessment for elderly patients suspected of pulmonary hypertension.

Background: The phenotype of patients seen for a suspicion of pulmonary hypertension has changed, with an increasing age and frequency of comorbidities. Selection of elderly patients, in whom a classical work-up is mandatory, is challenging. Comprehensive geriatric assessment (CGA) has modified the management of elderly patients with cancer.

DLNO/DLCO ratio evolution under targeted therapy in patients with pulmonary hypertension.

The ratio of the diffusing capacity of the lung for carbon monoxide (DLCO) and for nitric oxide (DLNO) measured simultaneously is modified in patients with precapillary pulmonary hypertension (PH). The potential impact of targeted therapy on the DLCO/DLNO ratio is unknown. Simultaneous measurements of DLNO and DLCO were performed at baseline, 3-4 month follow-up (first evaluation) and 12-month follow-up (second evaluation) after initiation of targeted PH therapies in incident cases of precapillary PH.

Long-term risk of postthrombotic syndrome after symptomatic distal deep vein thrombosis: The CACTUS-PTS study.

Background: After a proximal lower limb deep vein thrombosis (DVT; involving popliteal veins or above), up to 40% of patients develop postthrombotic syndrome (PTS) as assessed by the Villalta scale (VS). Poor initial anticoagulant treatment is a known risk factor for PTS. The risk of developing PTS after isolated distal DVT (infra-popliteal DVT without pulmonary embolism), and the impact of anticoagulant treatment on this risk, are uncertain.

Monitoring of biological response to clopidogrel after treatment for non-cardioembolic ischemic stroke or transient ischemic attack.

Background And Purpose: Biological response to clopidogrel prescribed after a non-cardioembolic ischemic stroke or transient ischemic attack (TIA) has been little studied. The aim of our study (AAPIX) was to assess this response and investigate the agreement between different biological assays in revealing poor responders.

Methods: Patients hospitalized following a non-cardioembolic ischemic stroke or transient ischemic attack (TIA) and prescribed clopidogrel were consecutively included from September 2013 to November 2015 in the Stroke Center of Saint-Etienne Hospital.

Chronic thromboembolic pulmonary hypertension suspicion after pulmonary embolism in cancer patients.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe condition which should be screened in patient with persistent dyspnea after pulmonary embolism (PE). After PE, CTEPH incidence was estimated between 0.1 and 9.

Role of platelet α2-adrenoreceptor in biological low response to Clopidogrel for patients with non cardioembolic ischemic stroke or transient ischemic attack.

Background And Purpose: Low biological response to Clopidogrel prescribed after non cardioembolic ischemic stroke or transient ischemic attack (TIA) is a major clinical problem and could explain the recurrence of vascular events. Platelet α2-adrenoreceptors are involved in the high residual platelet reactivity in stable coronary artery disease patients on dual antiplatelet therapy. In the present study we investigated the impact of platelet α2-adrenoreceptors on ADP-induced platelet aggregation and on ADP-induced platelet membrane CD62P (P-selectin) expression, a marker of platelet activation on blood samples from patients hospitalized at the acute phase of a non cardioembolic ischemic stroke or TIA.

Assessment of a flow cytometry technique for studying signaling pathways in platelets: Monitoring of VASP phosphorylation in clinical samples.

A recently released kit (PerFix EXPOSE) was reported to improve the measurement of the degree of phosphorylation of proteins in leukocytes by flow cytometry. We tested its adaptation for platelets to monitor vasodilator-stimulated phosphoprotein (VASP) phosphorylation, which is the basis of a currently used test for the assessment of the pharmacological response to P2Y12 antagonists (PLT VASP/P2Y12). The PerFix EXPOSE kit was compared to the PLT VASP/P2Y12 kit by using blood samples drawn at 24 h post clopidogrel dose from 19 patients hospitalized for a non-cardio-embolic ischemic stroke and treated with clopidogrel monotherapy for at least five days in an observational study.

Screening cancer after venous thromboembolism: How many abnormal tests before diagnosing cancer? An analysis of practice.

Introduction: Since Trousseau, we knows that venous thrombemboembolism (VTE) can reveal occult cancer. Different strategies of cancer screening have been evaluated: they are often time-consuming, cause stress and anxiety, and frequently require second-look examinations (due to the risk of false positives), with ultimately a very low yield (about 5%). We evaluated the number of suspect cancer tests before reporting them to the number of cancers finally diagnosed, after a VTE, in the setting of practice's analysis.

Effect of Activated Charcoal on Rivaroxaban Complex Absorption.

Objective: To quantify the impact of activated charcoal (AC) on rivaroxaban exposure in healthy volunteers.

Methods: This was an open-label study with an incomplete cross-over design of single-dose rivaroxaban (40 mg) administered alone or with AC in 12 healthy volunteers. The study comprised three treatment periods in randomised sequence, one with rivaroxaban administered alone and two with AC given at 2, 5 or 8 h post-dose.

Limited screening with versus without (18)F-fluorodeoxyglucose PET/CT for occult malignancy in unprovoked venous thromboembolism: an open-label randomised controlled trial.

Background: Clear guidelines for the investigation of occult malignancy after unprovoked venous thromboembolism are not yet available. (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT could serve as a comprehensive screening strategy for occult malignancy in this context. We aimed to compare a screening strategy based on (18)F-FDG PET/CT with a limited screening strategy for detection of malignant disease in patients with unprovoked venous thromboembolism.

[Thromboprophylaxis in medical patients: Which modifications with the new oral anticoagulants?].

Thromboprophylaxis with low molecular weight heparin or fondaparinux is associated with a 50% reduction in the risk of venous thrombo-embolism (VTE) in medical patients. Thromboprophylaxis is indicated in the prevention of VTE in medical patients at risk of VTE. Extended thromboprophylaxis with apixaban is associated with a greater reduction in VTE events but also with an increase in bleeding events when compared to standard therapy with enoxaparine.

A semi-mechanistic absorption model to evaluate drug-drug interaction with dabigatran: application with clarithromycin.

Aim: The aim of this study was to develop a PK/PD model to assess drug-drug interactions between dabigatran and P-gp modulators, using the example of clarithromycin, a strong inhibitor of P-gp.

Methods: Ten healthy male volunteers were randomized to receive in the first treatment period a single 300 mg dose of dabigatran etexilate (DE) and in the second treatment period 500 mg clarithromycin twice daily during 3 days and then 300 mg DE plus 500 mg clarithromycin on the fourth day, or the same treatments in the reverse sequence. Dabigatran plasma concentration and ecarin clotting time (ECT) were measured on 11 blood samples.