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Cancer-associated venous thromboembolism (CAT) is common in patients with cancer and associated with significant morbidity and mortality. The incidence of CAT continues to rise, complicating patient care and burdening healthcare systems. Patients with cancer experiencing VTE face poorer prognoses, making prevention and effective management imperative. This narrative review synthesizes evidence on thromboprophylaxis in ambulatory patients with cancer receiving systemic therapy and acute treatment strategies for CAT. Risk assessment models (e.g., Khorana score) aid in identifying high-risk patients who may benefit from thromboprophylaxis. Pharmacological thromboprophylaxis with low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) has been shown to reduce the risk of CAT without significantly increasing the risk of bleeding complications. However, implementation of risk-based strategies remains limited in clinical practice. For acute CAT management, LMWHs have been the standard of care, but DOACs are increasingly favored due to their convenience and efficacy. However, challenges persist, including bleeding risks and drug interactions. Emerging therapies targeting Factor XI inhibitors present promising alternatives, potentially addressing current limitations in anticoagulation management for CAT., Competing Interests: Declaration of competing interest MC reports personal fees from Leo Pharma, BMS, Pfizer, Sanofi, Valeo, Servier, and Bayer, and grant from Leo Pharma, BMS and Pfizer. LB reports personal fees and non-financial support from BMS/Pfizer, Leo Pharma, and Viatris, grants from Bayer, grants, personal fees and non-financial support from MSD, outside the submitted work. SL reports personal fees from Ferring, Pfizer and Lilly, outside the submitted work. PG reports personal fees or travelling expenses from Leo Pharma, BMS-Pfizer and Bayer. PM reports personal fees from Bayer Healthcare, BMS/Pfizer and Sanofi. IM reports grants, personal fees and non-financial support from BMS-Pfizer Alliance and Leo Pharma, personal fees from Sanofi, personal fees and non-financial support from Astra-Zeneca, outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Venous thromboembolism (VTE) presents a notable healthcare burden, particularly among the elderly, who experience increased risks and more severe complications. This review aims to use the extensive data from the RIETE registry, a comprehensive database on consecutive patients with VTE. We examine the clinical features, therapeutic approaches, and patient outcomes of VTE in elderly patients, compared to younger patients, offering a comprehensive understanding of management challenges and emphasizing the need for strategies that accommodate the unique challenges of this population., Competing Interests: Disclosures The authors declare they have no disclosure for this specific article., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data, on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with CAT on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR<30mL/min/1.72m 2 , the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (<50,000 platelets/μL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Many patients with cancer require palliative care at some stage and the vast majority of people followed in palliative care are cancer patients. Patients with cancer are at high risk of venous thromboembolism (VTE), and this is particularly true during the advanced palliative phase when mobility is limited or absent. Patients with cancer in palliative cancer are at higher bleeding risk compared to non-cancer patients. Decisions to treat VTE or withhold anticoagulation for these patients have proven to be difficult and depend largely on an individual clinician's judgment. For this reason, we have developed a consensus proposal for appropriate management of cancer-associated thromboembolism (CAT) in patients in palliative care, which is presented in this article. The proposal was informed by the recent scientific literature retrieved through a systematic literature review. In cancer patients in advanced palliative care, the benefit-risk ratio of anticoagulation seems unfavourable with a higher haemorrhagic risk than the benefit associated with prevention of CAT recurrence and, above all, in the absence of any benefit on quality of life. For this reason, we recommend that patients should be prescribed anticoagulants on a case-by-case basis. The choice of whether to treat, and with which type of treatment, should take into account anticipated life expectancy and patient preferences, as well as clinical factors such as the estimated bleeding risk, the type of VTE experienced and the time since the VTE event., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Venous thromboembolism (VTE) is a frequent and potentially fatal complication in patients with cancer. During the initial period after the thromboembolic event, a patient receiving anticoagulant treatment is exposed both to a risk of VTE recurrence and also to an elevated bleeding risk conferred by the treatment. For this reason, the choice of anticoagulant is critical. The choice should take into account patient-related factors (such as functional status, age, body mass index, platelet count and renal function), VTE-related factors (such as severity or site), cancer-related factors (such as activity and progression) and treatment-related factors (such as drug-drug interactions), which all potentially influence bleeding risk, and patient preference. These should be evaluated carefully for each patient during a multidisciplinary team meeting. For most patients, apixaban or a low molecular-weight heparin is the most appropriate initial choice for anticoagulant treatment. Such treatment should be offered to all patients with active cancer for at least six months. The patient and treatment should be re-evaluated regularly and anticoagulant treatment changed when necessary. Continued anticoagulant treatment beyond six months is justified if the cancer remains active or if the patient experienced recurrence of VTE in the first six months. In other cases, the interest of continued anticoagulant treatment may be considered on an individual patient basis in collaboration with oncologists., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: The time-course response after a single injection of botulinum toxin (BoNT) for post-stroke spasticity is debated. We addressed this issue by conducting a systematic review and a pharmacodynamic model-based meta-analysis., Methods: We searched Medline, PeDro and Google Scholar databases up to March 2020, selecting randomized controlled trials of post-stroke and traumatic brain injury patients with arm or leg muscle hypertonia, comparing BoNT to placebo, or different BoNT preparations. The main outcome was change in Modified Ashworth Scale (MAS) score. A non-linear mixed effect model was used to estimate maximal toxin and placebo effects (Emax and EPlacebo), the effect disappearance half-life (T1/2off) of BoNT and the doses achieving 50 and 80% of Emax (D50 and D80). The equivalence ratios between different BoNT preparations were calculated from D50 values. Adverse events were recorded., Results: Altogether, 2,236 unique records were screened by 2 independent reviewers: 35 eligible trials including 3011 patients (95% post-stroke) were identified. For all BoNT preparations, the BoNT Emax of -1.11 (95% credible interval -1.31; -0.29) was reached at 5 weeks; the maximal placebo effect was -0.30 (-0.37; -0.22). Both D50 and D80 differed significantly by muscle volume. At D50, the equivalence ratio was significantly higher for abobotulinumtoxinA (3.35) than onabotulinumtoxinA and lower for letibotulinumtoxinA (0.41). T1/2off was longer for abobotulinumtoxinA than for onabotulinumtoxinA and the other preparations (13.1 weeks [95% credible interval 7.7; 19.3] vs 8.6 weeks [7.1; 10.1]). Adverse events were minor, with a weak, but significant, dose-response relation for muscle weakness., Conclusions: This first pharmacodynamic model-based meta-analysis of individuals with stroke revealed that for all BoNT-A preparations, BoNT-A injections to treat spasticity have maximal effect at 5 weeks. The T1/2off was longer for abobotulinumtoxinA than other preparations. Differences between certain BoNT unit scales were also confirmed., Competing Interests: Declaration of Competing Interest Pascal Giraux and Etienne Ojardias received meeting sponsorship from Allergan, Ipsen, and Merz and compensation for consulting from Merz. Etienne Ojardias received through his institution a research support grant from Merz. Pascal Giraux is a co-founder of the Dessintey company. The other authors declare no conflict of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Proton pump inhibitors (PPIs) have improved the management and prevention of digestive diseases, leading to a heavy prescription of this therapy. In 2015, nearly one quarter of the French population had consumed a PPI and half of them were long-term users. The main objective of this study was to analyze, in patients hospitalized in several medical departments, the adequacy of long-term PPI prescriptions to recommendations., Method: The Use and management of proton pump inhibitors: an observational study project (UTOPPIA) is a longitudinal observational study conducted at the University Hospital of Saint-Étienne in the departments of hepato-gastroenterology, infectious and tropical diseases, internal medicine, vascular medicine and nephrology. All patients with PPI treatment on their usual outpatient prescription were interviewed., Results: Over a 3-month period, 334 of hospitalized patients (30.7%) had received a long-term PPI prescription and 181 patients (54.2%) could be included in the study for a total of 274 indications. Ninety-nine patients (54.7%) had a long-term PPI prescription in accordance with the recommendations. The most frequent indication (70 prescriptions) was the prescription of an antiplatelet drug or anticoagulant for subjects at high risk of bleeding in 70 prescriptions. Fifty-three PPI treatments were amended during the hospital stay, including 9 discontinuations. The justification for the change was documented in the patients' chart in only 17% of cases. Individual interviews of patients revealed that 75.1% of them were in favour of discontinuing their PPI treatment., Conclusions: About one-third of hospitalized patients in medical wards in France have long-term PPI treatment and half of these prescriptions do not comply with good practice recommendations. A majority of patients report being willing to try to stop PPI therapy., (Copyright © 2020 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

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., Methods: We studied retrospectively patients hospitalized for a VTE and with a cancer screening, between 2011 and 2012. Screening cancer was defined by performing at least one of the following tests: PSA, fecal occult blood test, mammography, abdominopelvic iconography (abdominal ultrasound and/or abdominal CT scan). We recorded the suspected cancer tests, the cancers diagnosed, their stage and the survival. These results were expressed as a percentage with a 95% confidence interval., Results: Out of the 491 patients treated for a VTE, screening cancer was performed on 295 patients (median age 66.2 years). Nineteen PSA (16.7%, 95% CI [10.3-25]) were abnormal, with 2 localized prostate cancers. Nineteen fecal occult blood tests (15.3%, 95% CI [9.5-23]) were positive, with 2 local cancers. Five mammograms suspected cancer (4.7% 95% CI [1.6-10.8]) for one confirmed. Thirty-eight abdomino-pelvic iconographies (14.4% 95% CI [10.4-19.2]) were suspect, with 7 confirmed cancers, 6 being metastatic at times of diagnostic., Conclusion: Among the 607 tests performed, 81 were suspected of cancer (13.3%) for only 12 cancers confirmed (2.0%). Screening cancer exposes patients to several false positive tests., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Non-vitamin K antagonist oral anticoagulants (NOACs) - dabigatran, rivaroxaban, apixaban and edoxaban - are well established in terms of preventing stroke or systemic embolism in patients with non-valvular atrial fibrillation and high thromboembolism risk. When prescribed incorrectly, NOACs are associated with an increased risk of ischaemic events and bleeding. Current NOAC labels explicitly address dose adjustments according to age, body weight, renal function and concomitant treatment with P-glycoprotein inhibitors. The required dose adjustments vary significantly from molecule to molecule, thereby creating a complex dose adjustment environment. Furthermore, recommendations support assessment of individual risk using thromboembolic and bleeding risk scores. Evidence-based medicine also provides data about specific patient profiles. In particular, some patients who are at higher risk of bleeding, such as patients on polymedication, are often at higher risk of stroke. More and more patients are being treated with NOACs. The question of appropriate dosing has become important, as studies are starting to show that reduced doses are being prescribed at very high rates. Although these data have not been evaluated in light of individual risk assessments, in everyday practice, physicians are often more concerned about drug-related bleeding than about the spontaneous evolution of the disease (stroke/systemic embolism), leading to high rates of prescription of inadequately low doses. Recent results have shown that only certain risk criteria justify dose reduction. Thus, the right dose needs to be prescribed for the right patient in order to obtain, in real-life practice, the benefits of NOACs that have been demonstrated in randomized clinical trials., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aim: Deep vein thrombosis (DVT) is a potential serious common disease. Its management is, except in particular cases, on an outpatient basis. General practitioner's (GP) role usually includes the treatment risk/benefit reassessment. The treatment duration can vary and is difficult to define. The national and international guidelines do not explain clearly when to refer, or not, to a vascular specialist in order to stop treatment. The study's objective was to identify, for DVT, when a GP has to refer or not to a vascular specialist, for anticoagulant withdrawal., Methods: A modified Delphi consensus study had been conducted by a panel of general practitioners and vascular specialists to identify, in which situations all clinicians agree that GPs can stop anticoagulation on their own and other situations in which GP have to refer to vascular specialists. Clinical situations and their respective duration of anticoagulant therapy have been identified by a DVT management guideline literature research., Results: After two rounds, a strong agreement had been reached for each clinical situation. For 7 clinical situations, GPs were able to stop anticoagulation on their own, for 13 clinical situations; it was necessary to refer to a vascular specialist. We obtained a consensus regarding 3 modulating factors., Discussion: Consensual situations, in which the general practitioners may be able to stop anticoagulation themselves, are isolated distal DVT without cancer and proximal DVT caused by a major reversible risk factor. Situations justifying a vascular medical advice were unprovoked DVT, DVT in a context of pregnancy, postpartum, cancer and proximal DVT in a context of hormonal therapy., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Real-life data is important in understanding the needs of patients in routine clinical practice, particularly owing to the fact that almost a quarter of patients with venous thromoboembolism (VTE) have at least one exclusion criterion preventing their recruitment into randomized clinical trials. The Registro Informatizado de Enfermedad Trombo Embólica (RIETE) registry is an ongoing, international, multicentre, prospective registry of consecutive patients presenting with acute VTE. In this chapter, we summarized some of the most relevant data concerning the epidemiology of VTE in the RIETE registry., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

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. Extended thromboprophylaxis with rivaroxaban is associated with a greater reduction in VTE events but also with an increase in bleeding events, when compared to standard therapy with enoxaparine. Rivaroxaban and apixaban are currently not indicated in medical prophylaxis., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Rivaroxaban (with initial increased dosage) may be used as a stand-alone therapy in patients with venous thrombo-embolism. The development of new anticoagulant drugs opened several options in the management of venous thrombo-embolism. The efficacy and safety of these new oral anticoagulants in specific population as elderly and those with renal impairment deserve future research. At that time, only rivaroxaban is licensed in France, in the treatment of deep venous thrombosis., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Vitamin K antagonists (VKA) had several decades of proven efficacy in AF-related stroke prevention but the drug's numerous limitations make its implementation difficult for practitioners and patients. The drawbacks of VKA have prompted the development of new oral anticoagulants (NOAC) that are at least as efficacious and safe as warfarin in phase III trials. Dabigatran (220 and 300mg/day), rivaroxaban (20mg/day) and apixaban (10mg/day) were proved to be non-inferior compared with warfarin in the prevention of bleeding, stroke and systemic embolism. Dabigatran 300mg/day and apixaban were found to be statistically superior to warfarin in stroke reduction. All these drugs reduced the risk of intracranial bleeding compared to warfarin. Dabigatran 220mg/day and apixaban decreased the risk of major bleeding. The limitation of NOAC was an increase of gastrointestinal bleeding by dabigatran 300mg/j and rivaroxaban and myocardial infarction by dabigatran. Practitioners must also be aware of the disadvantages of these new drugs when choosing NOAC for their patients with unstable INR., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)