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International audience; Due to concomitant changes in pro- and anti-coagulant mechanisms, patients with liver dysfunction have a “rebalanced hemostasis”, which can easily be tipped toward either a hypo- or a hypercoagulable phenotype. Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities. Conventional coagulation screening tests, such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures. The introduction of global coagulation assays, such as viscoelastic testing (VET), has been an important step forward in the assessment of the overall hemostasis profile. A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings. The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.

INTRODUCTION We aimed to evaluate the performance of the fully automated multiparameter CN-6000 hemostasis analyzer. METHODS Performance evaluation of the CN-6000 analyzer was conducted for 10 tests including prothrombin time (PT), activated partial prothrombin time (aPTT), fibrinogen level, anti-Xa activity, and antithrombin activity using a unique portfolio of liquid ready-to-use reagents. Precision, sample and reagent carryovers, throughput, and sample turnaround time (STAT) function were prospectively assessed. Results from 343 samples (normal subjects, critically ill patients, patients receiving anticoagulants, subjects with high or low fibrinogen levels, and patients with decreased levels of factor II, V, VII, and X) were compared to those obtained on the STA-R Max 2® analyzer using dedicated reagents. RESULTS Total precision (coefficient of variation) was below 7% for all parameters in both normal and pathological ranges. For all analyzed parameters, results obtained on the CN-6000 were strongly correlated with those obtained on the STA-R Max 2®analyzer. Agreement between both instruments was excellent for all assays. The CN-6000 demonstrated a 30% higher throughput compared to the STA-R Max 2® (258 vs 185 tests per hour for a panel of tests including PT, aPTT, fibrinogen, factor V, anti-Xa, and D-Dimer). STAT turnaround time for critical care samples testing was

Updated clinical practice guidelines recommend the long-term use of low-molecular-weight heparins or direct oral anticoagulants as the preferred option for the treatment of cancer-associated thrombosis (CAT), using a personalized approach matching the right drug to the right patient. In most cases, the benefit of anticoagulant therapy outweighs the risk. However, the long-term use of anticoagulants is associated with a non-negligible risk of bleeding, which constitutes a rare but serious adverse effect. Bleeding complications have been reported to be overall 2 to 3 times more frequent in cancer patients with CAT receiving anticoagulation than in non-cancer patients, with a reported incidence of major bleeding ranging from 2.4 to 16.0% in randomized controlled trials (RCT). In the absence of validated risk assessment model to predict the risk of bleeding in these patients, a careful evaluation of each individual profile, with adequate selection of the most appropriate anticoagulant for each individual patient, is warranted for overcoming management challenges, taking in account the numerous factors which may potentiate the overall bleeding risk in these complex patients, such as advanced or metastatic disease, older age, anemia, thrombocytopenia, renal impairment, liver dysfunction, and concomitant anticancer therapies. The purpose of this review is to call for awareness on bleeding complications as a major safety issue of CAT treatment and to summarize data from recent RCT and real-world studies on the incidence and risk factors for bleeding in this unique and challenging population to further help clinicians in decision-making.

Summary Introduction Treatment of cancer-associated thrombosis (CAT) requires specific approaches, although it is well codified in most cases. Current national and international (International Initiative on Cancer and Thrombosis, ITAC) Clinical Practice Guidelines (CPG) recommend the use of low-molecular-weight heparin (LMWH) over 6 months as first treatment option, and anticoagulation should be maintained thereafter as long as cancer is active. Since compliance improves when patients understand their disease and related treatments, we created a dedicated patient education program (PEP) for CAT, aiming to improve quality of care. Methods Retrospective analysis of all patients who voluntarily joined the PEP for CAT from 2014 to 2020. Results In total, 182 cancer patients (median age, 64.9 years) were included, 53.3% with metastatic disease. A total of 528 PEP sessions (median, 3 per patient) were delivered. After PEP completion, the rate of self-injections or those performed at home by a relative had increased from 49.1% to 59.8% (P = 0.05). Quality of life had improved significantly (P = 0.025) and 90.0% of patients reported adhering to anticoagulant therapy. Conclusion Implementation of a structured and personalized PEP for CAT is feasible, allowing to improve cancer patient empowerment, adherence to CAT treatment and quality of life. The Groupe francophone et cancer (GFTC) members aim at facilitating access to CAT-PEP for both patients and caregivers and use of the multi-language ITAC-CPG mobile app (free access: www.itaccme.com ) to improve the care and quality of life of patients with CAT.

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35–56) years, with a median body mass index of 30 (27–35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8–16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin–antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p

Introduction Les patients ayant un cancer solide ou hématologique ont été considérés comme étant plus susceptibles de contracter une infection à SARS-COV-2, et de développer plus fréquemment des complications graves. Nous avons voulu comparer les caractéristiques cliniques et le pronostic des patients atteints de COVID-19 avec ou sans cancer. Méthodes Il s’agit d’une étude observationnelle de cohorte prospective, de tous les patients hospitalisés consécutivement dans une unité dédiée aux patients atteints de COVID-19 à l’hôpital de la Pitié-Salpêtrière à Paris, entre le 16 mars et le 26 avril 2020. Résultats Parmi les 262 patients hospitalisés pour un diagnostic de COVID-19 dans cette unité lors de la première vague de la pandémie, 62 étaient également suivis pour un cancer solide ou hématologique actif. Il n’y avait pas de différence significative entre les deux groupes en ce qui concerne leurs caractéristiques cliniques, les comorbidités, ou leur pronostic entre ces deux groupes. On retrouvait cependant significativement plus de patients qui avaient une lymphopénie (médiane (IQ) : 0,7 (0,5–1,1) versus 0,9 (0,7–1,3)), et qui avaient été contaminés en milieu hospitalier (35,5 % versus 18 %, p = 0,008). Conclusions Les patients oncologiques et non oncologiques hospitalisés pour COVID-19 présentaient des résultats similaires en termes de décès, d’admission en soins intensifs ou de thrombose/hémorragie. Ils devraient bénéficier de la même stratégie thérapeutique que la population générale pendant la pandémie de COVID-19.

Background Meta-analyses are widely used to strengthen available evidence and obtain more precise estimates of treatment effect than any individual trial. Paradoxically, multiplication of meta-analyses on the same topic can lead to confusion as practitioners no longer benefit from a rapid and synthetic response. This phenomenon may appear disproportionate when the number of published meta-analyses exceeds the number of original studies. Objectives To describe an example of redundant meta-analyses published in the same area with the same randomized clinical trials (RCTs). Methods A systematic review was performed to identify all published meta-analyses of original RCTs that compared direct oral anticoagulants with low molecular weight heparins in cancer patients with venous thromboembolism (VTE). Forest plots were used to represent the meta-analyses results for efficacy (VTE recurrence) and safety (major bleeding) endpoints. An authors' network was constructed to explore the links between the authors of the published meta-analyses. Results In the past 3 years, four original RCTs were the subject of 20 published meta-analyses by 142 authors: five, four, and 11 meta-analyses pooled the data of two, three, and four RCTs, respectively. The results of meta-analyses were similar regarding the risks of VTE recurrence and major bleeding. The 11 meta-analyses of four RCTs were published within 6 months of the publication of the last RCT. Conclusions The epidemic proportions of such redundant literature and authorship could be moderated by developing "living" meta-analyses and encouraging authors of new RCTs to update the corresponding meta-analysis in the same paper as their original research.

Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty-eight (74 [36-100] years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow-up (7 [0·2-48.7] months). At diagnosis, FV was10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) [0·36-0·80], P 0·05}. Bleeding onset during follow-up was associated with a slow AFVI clearance (P 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29-100) and a specificity of 86% (95% CI: 57-98, P = 0·02). Kaplan-Meier analysis showed that AFVI clearance7 months increased the risk of bleeding by 8 (95% CI: [0·67-97], P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow-up are both associated with bleeding in patients with AFVI.

The Ottawa score (OS) for predicting the risk of recurrent venous thromboembolism (VTE) in cancer patients with VTE may help to guide anticoagulant treatment decisions that will optimize benefit-risk ratios. However, data on its reliability are conflicting. We applied the OS to all cancer patients with VTE enrolled in the prospective multicenter TROPIQUE study who received low-molecular-weight heparin over a 6-month period. Of 409 patients, 171 (41.8%) had a high-risk OS. The 6-month cumulative incidence of recurrent VTE was 7.8% (95%CI 4.2–14.8) in the high-risk OS group versus 4.8% (95%CI 2.6–8.9) in the low-risk OS group (SHR 1.47; 95%CI 0.24–8.55). The Area Under the Receiver Operating Characteristic curve (AUROC) of the OS in identifying patients who developed recurrent VTE was 0.53 (95%CI 0.38–0.65), and its accuracy was 57.9%. Among individual variables included in the OS, only prior VTE was significantly associated with the 6-month risk of recurrent VTE (SHR 4.39; 95% CI 1.13–17.04). When pooling data from all studies evaluating this score for predicting VTE recurrence in cancer patients (7 studies, 3413 patients), the OS estimated pooled AUROC was 0.59 (95%CI 0.56–0.62), and its accuracy was 55.7%. The present findings do not support the use of the OS to assess the risk of recurrent VTE in cancer patients.

International audience; Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is increasingly used in Coronavirus disease-19 (COVID-19) patients with the most severe forms of acute respiratory distress syndrome (ARDS). Its use is associated with a significant hemostatic challenge, especially in COVID- 19 patients who have been demonstrated to otherwise present a COVID-19-associated coagulopathy. The systematic use of unfractionated heparin therapy to prevent circuit thrombosis is warranted during ECMO support. The clinical presentation and management of heparin-induced thrombocytopenia, which is a rare but life-threatening complication of heparin therapy, has not been described in those patients yet. We report herein two cases of laboratory-confirmed HIT in COVID-19 patients with severe ARDS admitted to our intensive care unit for VV-ECMO support and the successful use of argatroban as an alternative therapy. We also provide a brief literature review of best evidence for managing such patients. The diagnosis and management of HIT is particularly challenging in COVID-19 patients receiving ECMO support. An increased awareness is warranted in those patients who already present a procoagulant state leading to higher rates of thrombotic events which can confuse the issues. Argatroban seems to be an appropriate and safe therapeutic option in COVID-19 patients with HIT while on VV-ECMO.

Resumen Los sindromes coronarios agudos estan vinculados en la gran mayoria de los casos a la ruptura de una placa ateromatosa que inicia la activacion y luego la agregacion plaquetaria que conduce al desarrollo de un trombo coronario mas o menos oclusivo. La prevencion de las recidivas isquemicas en los pacientes de riesgo se basa en gran medida en el uso de antiagregantes plaquetarios, agentes farmacologicos que inhiben la activacion de las plaquetas o, en raras ocasiones, directamente su agregacion. La presencia de una enfermedad coronaria requiere el uso de uno o incluso dos antiagregantes. Por ejemplo, a un paciente que se someta a una angioplastia coronaria y/o que haya tenido un sindrome coronario agudo se le prescribira una doble terapia compuesta por aspirina (que inhibe la activacion de las plaquetas por la via de la ciclooxigenasa) y un inhibidor del receptor P2Y12 del difosfato de adenosina. Este ultimo puede ser clopidogrel, prasugrel o ticagrelor. Estas dos ultimas moleculas han demostrado su superioridad sobre el clopidogrel en pacientes con sindrome coronario agudo, pero a costa de un mayor riesgo de episodios hemorragicos. Las hemorragias (digestivas, intracraneales, etc.) son las principales reacciones adversas asociadas a los agentes antiplaquetarios. Deben buscarse en el paciente en tratamiento, pero sobre todo deben anticiparse. Uno de los principales desafios de la cardiologia moderna es determinar los riesgos isquemicos/tromboticos y hemorragicos de cada paciente coronario para ajustar la intensidad del tratamiento antiplaquetario (numero y potencia de los agentes antiagregantes), asi como la duracion del tratamiento a los perfiles encontrados; ahora es el momento mas oportuno para el tratamiento personalizado.

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

We read with great interest the comment by Suarez-Perez et al. on our article.[1] We share their concerns regarding the need for a cautious interpretation of antiphospholipid antibodies (aPLA) positivity in patients with coronary virus disease 2019 (COVID-19). Herein, we would like to add further insights in the discussion.

Coronavirus disease 2019 (COVID‐19) is associated with both severe systemic inflammation and a prothrombotic state, as reflected by significant increases in fibrinogen and D‐dimers levels that have been associated with poor prognosis and high rates of severe pulmonary embolism. A recent report suggested a role for antiphospholipid antibodies (aPLA) in the thrombotic manifestations associated with severe COVID‐19. As we also recently noticed unexplained lengthening of activated partial thromboplastin time (aPTT) in some critically ill COVID‐19 patients, we explored our patients for aPLA positivity.

Background A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting. Objectives We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI. Methods We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction, stroke, and urgent revascularization. Results We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥2 or with MACE (p = 0.12 and p = 0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor when it was analyzed qualitatively (low on-treatment PR [LTPR] vs. no LTPR). Conclusion On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.

International audience; COVID-19 is associated with encephalitis in critically ill patients and endothelial dysfunction seems to contribute to this life-threatening complication. Our objective was to determine the hallmark of endothelial activation in COVID-19 related encephalitis.In an observational study in intensive care unit (ICU), we compared vascular biomarkers of critically ill COVID-19 patients with or without encephalitis. To be classified in the Encephalitis group, patients had to have new onset of central neurologic symptom, and pathological findings on either brain magnetic resonance imaging (MRI) and/or electroencephalogram (EEG).Among the 32 critically ill COVID-19 consecutive patients, 21 were categorized in the Control group and 11 in the Encephalitis group. Encephalitis patients had a longer ICU-stay than Control patients (median length [25th-75th percentile] of 52[16-79] versus 20.5[11-44] days respectively, p=0.04). Nine-months overall follow-up mortality reached 21% (7/32 patients), with mortality rates in the Encephalitis-group and the Control group of 27% and 19% respectively. Encephalitis was associated with significant higher release of soluble endothelial activation markers (sE-selectin, Tumor-Necrosis-Factor-α (TNF-α), Interleukin-6, Placental Growth Factor and Thrombomodulin), but these increases were correlated with TNF-α plasmatic levels. The hypoxia-inducible protein Angiopoietin-like-4 (ANGPTL4) was at significantly higher levels in Encephalitis patients compared to Control patients (p=0.0099), and in contrary to the other increased factors, was not correlated with TNF-α levels (r=0.2832, p=0.1163).Our findings suggest that COVID-19 related encephalitis is a cytokine-associated acute brain dysfunction. ANGPTL4 was the only elevated marker found in Encephalitis patients, which was not correlated with systemic inflammation, suggesting that ANGPTL4 might be a relevant factor to predict encephalitis in critically ill COVID-19 patients

Summary Introduction The Coronavirus disease-2019 outbreak (COVID-19) has been declared a pandemic by the World Health Organization. Studies report both a severe inflammatory syndrome and a procoagulant state in severe COVID-19 cases, with an increase of venous thromboembolism, including pulmonary embolism (PE) and deep vein thrombosis (DVT). In this context, we discuss the use of doppler ultrasonography (DUS) in the screening and diagnosis of DVT in ambulatory and hospitalized patients with, or suspected of having, COVID-19, outside the intensive care unit (ICU). Material and methods Non-systematic review of the literature. Results In patients hospitalized for or suspected of COVID-19 infection with the presence of either (a) DVT clinical symptoms, (b) a strong DVT clinical probability (Wells score > 2) or (c) elevated D-dimer levels without DVT clinical symptoms and without PE on lung CT angio-scan, DVT should be investigated with DUS. In the presence of PE diagnosed clinically and/or radiologically, additional systematic DVT screening using DUS is not recommended during the COVID-19 pandemic. The use of 4-points compression DUS for DVT screen and diagnosis is the most appropriate method in this context. Discussion Systematic DUS for DVT screening in asymptomatic COVID patients is not recommended unless the patient is in the ICU. This would increase the risk of unnecessarily exposing medical staff to SARS-CoV-2 and monopolizing limited resources during this period.

International audience

The management of cancer-associated thrombosis (CAT) poses unique challenges to healthcare professionals. While low-molecular weight heparins (LMWHs) have long been the gold standard for both the primary and secondary prevention of CAT, results from large randomized controlled trials assessing the benefit of direct oral anticoagulants (DOACs) in both settings have resulted in some paradigm shifts. Herein, we review and compare recommendations from the latest authoritative clinical practice guidelines (CPGs) for the management of CAT and summarize the most recent evidence on available treatment options. A rigorous methodology was used to select high quality CPGs and compare the recommendations across CPGs. Only CPGs focusing on the management of CAT developed by a multidisciplinary international working group and issued or endorsed by national or international scientific societies, or government organizations were eligible for inclusion. The quality of selected CPGs was assessed using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) tool. Four CPGs met the inclusion criteria, including the International Initiative on Thrombosis and Cancer (ITAC), the American Society of Clinical Oncology (ASCO), the American Society of Hematology (ASH), and the National Comprehensive Cancer Network (NCCN).

International audience; The management of cancer-associated thrombosis (CAT) is an evolving area. With the use of direct oral anticoagulants as a new option in the management of CAT, clinicians now face several choices for the individual cancer patient with venous thromboembolism. A personalized approach, matching the right drug to the right patient, based on drug properties, efficacy and safety, side effect profile of each drug, and patient values and preference, will probably supplant the one size fits all approach of use of only low-molecular-weight heparin in the near future. We herein present eight translational, clinical research, and review articles on recent advances in the management of CAT published in the Special Issue "Treatment for Cancer-Associated Thrombosis" of Cancers. For now, a multidisciplinary patient-centered approach involving a close cooperation between oncologists and other specialists is warranted to guide clinical decision making and optimize the treatment of VTE in cancer patient.

International audience; Background: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts.Objectives: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19.Methods: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI).Results: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59μg/L (95% CI 2.79-4.40μg/L), and the Z-score for overall effect was 8.74 (P

Patients with pancreatic cancer (PC) carry the highest risk of venous thromboembolism (VTE) amongst all cancer patients. Appropriate use of primary thromboprophylaxis might significantly and safely reduce its burden. We performed a systematic review of published studies and meeting abstracts using MEDLINE and EMBASE through July 2020 to evaluate the efficacy and safety of primary thromboprophylaxis in ambulatory PC patients receiving chemotherapy. The Mantel&ndash, Haenszel random effect model was used to estimate the pooled event-based risk ratio (RR) and the pooled absolute risk difference (RD) with a 95% confidence interval (CI). Five randomized controlled studies with 1003 PC patients were included in this meta-analysis. Compared to placebo, thromboprophylaxis significantly decreased the risk of VTE (pooled RR 0.31, 95% CI 0.19&ndash, 0.51, p &lt, 0.00001, I2 = 8%, absolute RD &minus, 0.08, 95% CI &minus, 0.12&ndash, &minus, 0.05, p &lt, 0.00001, I2 = 0%), with an estimated number needed to treat of 11.9 patients to prevent one VTE event. Similar reductions of VTE were observed in studies with parenteral (RR 0.30, 95% CI 0.17&ndash, 0.53) versus oral anticoagulants (RR 0.37, 95% CI 0.14&ndash, 0.99) and in studies using prophylactic doses of anticoagulants (RR 0.34, 95% CI 0.17&ndash, 0.70) versus supra-prophylactic doses of anticoagulants (RR 0.27, 95% CI 0.08&ndash, 0.90). The pooled RR for major bleeding was 1.08 (95% CI 0.47&ndash, 2.52, p = 0.85, I2 = 0%) and the absolute RD was 0.00 (95% CI &minus, 0.02&ndash, 0.03, p = 0.85, I2 = 0%). Evidence supports a net clinical benefit of thromboprophylaxis in ambulatory PC patients receiving chemotherapy. Adequately powered randomized phase III studies assessing the most effective anticoagulant and the optimal dose, schedule and duration of thromboprophylaxis to be used are warranted.

The high neutrophil to lymphocyte ratio observed in critically ill patients with COVID-19 is associated with excessive levels of reactive oxygen species (ROS), which promote a cascade of biological events that drive pathological host responses. ROS induce tissue damage, thrombosis and red blood cell dysfunction, which contribute to COVID-19 disease severity. We suggest that free radical scavengers could be beneficial for the most vulnerable patients. In this Comment article, Becker and colleagues consider how the excessive release of reactive oxygen species by neutrophils may perpetuate red blood cell dysfunction, thrombosis and tissue damage in severe cases of COVID-19.

Background: Percutaneous left atrial appendage closure (LAAC) exposes to the risk of device thrombosis in patients with atrial fibrillation who frequently have a contraindication to full anticoagulation. Thereby, dual antiplatelet therapy (DAPT) is usually preferred. No randomized study has evaluated nonvitamin K antagonist oral anticoagulant after LAAC, and we decided to evaluate the efficacy and safety of reduced doses of rivaroxaban after LAAC. Methods: ADRIFT (Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban in Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure) is a multicenter, phase IIb study, which randomized 105 patients after successful LAAC to either rivaroxaban 10 mg (R 10 , n=37), rivaroxaban 15 mg (R 15 , n=35), or DAPT with aspirin 75 mg and clopidogrel 75 mg (n=33). The primary end point was thrombin generation (prothrombin fragments 1+2) measured 2 to 4 hours after drug intake, 10 days after treatment initiation. Thrombin-antithrombin complex, D-dimers, rivaroxaban concentrations were also measured at 10 days and 3 months. Clinical end points were evaluated at 3-month follow-up. Results: The primary end point was reduced with R 10 (179 pmol/L [interquartile range (IQR), 129–273], P 15 (163 pmol/L [IQR, 112–231], P 10 and R 15 while rivaroxaban concentrations increased significantly from 184 ng/mL (IQR, 127–290) with R 10 to 274 ng/mL (IQR, 192–377) with R 15 , P Conclusions: Thrombin generation measured after LAAC was lower in patients treated by reduced rivaroxaban doses than DAPT, supporting an alternative to the antithrombotic regimens currently used after LAAC and deserves further evaluation in larger studies. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03273322.

International audience; Direct oral anticoagulants (DOAC) are now recommended for the treatment of cancer-associated thrombosis (CAT) based on the results of dedicated trials demonstrating that DOAC are non-inferior to low molecular weight heparins in preventing recurrent venous thromboembolism (VTE) in this population. The definition of "cancer patient" differs substantially among studies. Whether patients with active cancer and those with a history of cancer (HOC) carry the same risks of recurrent VTE and bleeding remains unclear. Few studies reported data on the efficacy and safety of anticoagulants according to active cancer or HOC categories. While in subgroup analyses of EINSTEIN and HOKUSAI the rates of recurrent VTE and bleeding did not differ between these categories, results from a subgroup analysis of AMPLIFY, from HOKUSAI-Cancer, and from the COMMAND cohort suggest that HOC patients might have a lower bleeding risk than active cancer patients. Whether the inclusion of HOC patients in CAT studies might introduce some bias by decreasing the rates of both recurrent VTE and bleeding remains an unanswered issue since no dedicated prospective study addressed this question. A strict definition of active cancer should be used in further trials.

International audience; Exocrine pancreatic ductal adenocarcinoma, simply referred to as pancreatic cancer (PC) has the worst prognosis of any malignancy. Despite recent advances in the use of adjuvant chemotherapy in PC, the prognosis remains poor, with fewer than 8% of patients being alive at 5 years after diagnosis. The prevalence of PC has steadily increased over the past decades, and it is projected to become the second-leading cause of cancer-related death by 2030. In this context, optimizing and integrating supportive care is important to improve quality of life and survival. Venous thromboembolism (VTE) is a common but preventable complication in PC patients. VTE occurs in one out of five PC patients and is associated with significantly reduced progression-free survival and overall survival. The appropriate use of primary thromboprophylaxis can drastically and safely reduce the rates of VTE in PC patients as shown from subgroup analysis of non-PC targeted placebo-controlled randomized trials of cancer patients and from two dedicated controlled randomized trials in locally advanced PC patients receiving chemotherapy. Therefore, primary thromboprophylaxis with a Grade 1B evidence level is recommended in locally advanced PC patients receiving chemotherapy by the International Initiative on Cancer and Thrombosis clinical practice guidelines since 2013. However, its use and potential significant clinical benefit continues to be underrecognized worldwide. This narrative review aims to summarize the main recent advances in the field including on the use of individualized risk assessment models to stratify the risk of VTE in each patient with individual available treatment options.

The high neutrophil to lymphocyte ratio observed in critically ill patients with COVID-19 is associated with excessive levels of reactive oxygen species (ROS), which promote a cascade of biological events that drive pathological host responses. ROS induce tissue damage, thrombosis and red blood cell dysfunction, which contribute to COVID-19 disease severity. We suggest that free radical scavengers could be beneficial for the most vulnerable patients., In this Comment article, Becker and colleagues consider how the excessive release of reactive oxygen species by neutrophils may perpetuate red blood cell dysfunction, thrombosis and tissue damage in severe cases of COVID-19.

Low molecular weight heparin (LMWH) for at least 3-6 months is the current standard of care for the treatment of cancer associated venous thromboembolism (VTE). Anticoagulation should be continued as long as the cancer is active. In recent years, several direct-acting oral anticoagulants (DOACs) have been approved for the treatment of VTE in the general population. These drugs have progressively emerged as attractive alternatives with the potential to overcome the limitations of LMWH. Due to the lack of high quality prospective data, DOACs are currently not recommended for the treatment of cancer associated VTE yet. Indeed, evidence supporting the use of DOACs in this specific population remains limited, and concerns have been raised about their safety and efficacy in this setting. However, a pattern of increased use of DOACs has been observed in the cancer population. Meta-analyses of Phase III trials of DOACs in VTE as well as analysis of large health care claims databases and non-controlled retrospective studies suggest that DOACs might have similar effectiveness and safety to LMWH for the management of cancer associated VTE. Results from 2 randomized clinical trial (RCT), HOKUSAI-Cancer and SELECT-D, were recently released. Based on a meta-analysis of these 2 RCTs, compared to LMWH, DOACs had lower 6 month recurrent VTE but higher major bleeding. Thus, DOACs should be used with caution in cancer patients and a careful evaluation of the risks and benefits for individual patients is warranted. Ongoing studies will provide much needed evidence to guide clinical care.

Pancreatic cancer (PC) is a devastating malignancy with an overall 5-year survival of 8% for all stages combined. Most of the PC patients diagnosed have an advanced disease (40%) or metastatic stage (40%), which eliminates surgery as a potentially curative treatment. The disease course is often complicated by venous thromboembolism (VTE) events, which per se account for significant morbidity and mortality, with significantly worsen survival. PC is associated with the highest risk of VTE among all cancer patients. We review the literature data to address the incidence and clinical outcomes of VTE in PC patients. VTE incidence varies from 5 to 41% according to epidemiological studies and is as high as 57% in postmortem series. Since 2013, international clinical practice guidelines recommend primary thromboprophylaxis with a grade 1B level of evidence as an adjuvant therapy in advanced PC. A recent meta-analysis of randomized controlled trials investigating the benefit and risk of low-molecular-weight heparins (LMWH) in ambulatory advanced PC patients under chemotherapy showed that the incidence of VTE was 2.1% in patients treated with LMWH and 11.2% in controls (risk ratio, 0.18; 95% CI, 0.083-0.39; P

International audience; Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size descriptors (BSD) on peak anti-Xa levels in BS obese patients receiving LMWH fixed doses to identify which one had the greatest impact. One hundred and thirteen BS obese patients [median body mass index (BMI), 43.3 kg/m(2) (IQR, 40.6-48.7 kg/m(2))] receiving subcutaneous dalteparin 5000 IU twice daily were included in this prospective monocenter study. Peak steady-state anti-Xa levels were measured peri-operatively following thromboprophylaxis initiation. Only 48% of patients achieved target anti-Xa levels (0.2-0.5 IU/ml). In univariate analysis, age, gender, total body-weight (TBW), lean body-weight (LBW), ideal body-weight (IBW), BMI and estimated glomerural filtration rate (eGFR) were associated with anti-Xa levels. The strongest negative association was observed with LBW (r=-0.56, p55.8 kg) had the highest sensitivity (73%) and specificity (69%) to predict sub-prophylactic anti-Xa levels. In multivariate analysis, LBW and eGFR remained associated with anti-Xa levels (beta=-0.47 +/- 0.08, p

International audience; Argatroban is a direct anti-IIa (thrombin) anticoagulant, administered as a continuous intravenous infusion; it has been approved in many countries for the anticoagulant management of heparin-induced thrombocytopaenia (HIT). Argatroban was recently proposed as the non-heparin anticoagulant of choice for the management of patients diagnosed with Vaccine-induced Immune Thrombotic Thrombocytopaenia (VITT). Immunoglobulins are also promptly intravenously administered in order to rapidly improve platelet count; concomitant therapy with steroids is also often considered. An ad hoc committee of the French Working Group on Haemostasis and Thrombosis members has worked on updated and detailed proposals regarding the management of anticoagulation with argatroban, based on previously released guidance for HIT, and adapted for VITT. In case of VITT, the initial dose to be preferred is 1.0 µg × kg(-1) × min(-1), with further dose-adjustments based on iterative and frequent clinical and laboratory assessments. It is strongly advised to involve a health practitioner experienced in the management of difficult cases in haemostasis. The first laboratory assessment should be performed 4 h after the initiation of argatroban infusion, with further controls at 2-4-h intervals until steady state, and at least once daily thereafter. Importantly, full anticoagulation should be rapidly achieved in case of widespread thrombosis. Cerebral vein thrombosis (which is typical of VITT) should not call for an overly cautious anticoagulation scheme. Argatroban administration requires baseline laboratory assessment and should rely on an anti-IIa assay to derive argatroban plasma levels using a dedicated calibration, with a target range between 0.5 and 1.5 µg/mL. Target argatroban plasma levels can be refined based on meticulous appraisal of risk factors for bleeding and thrombosis, on frequent reassessments of clinical status with appropriate vascular imaging, and on the changes in daily platelet counts. Regarding the use of aPTT, baseline value and possible causes for alterations of the clotting time must be taken into account. Specifically, in case of VITT, an aPTT ratio (patient’s/mean normal clotting time) between 1.5 and 2.5 is suggested, to be refined according to the sensitivity of the reagent to the effect of a direct thrombin inhibitor. The sole use of aPTT is discouraged: one has to resort to a periodical check with an anti-IIa assay at least, with the help of a specialised laboratory if necessary. Dose modifications should proceed in a stepwise manner with 0.1 to 0.2 µg × kg(-1) × min(-1) up- or downward changes, taking into account the initial dose, laboratory results, and the whole individual setting. Nomograms are available to adjust the infusion rate. Haemoglobin level, platelet count, fibrinogen plasma level and liver tests should be periodically checked, depending on the clinical status, the more so when unstable.

Venous thromboembolism (VTE) is a frequent and serious complication in cancer patients, and the second leading cause of death in this setting. Cancer patients are also more likely to present recurrent VTE and major bleeding while taking anticoagulants. Management of VTE in these patients is always challenging and remains suboptimal worldwide. In 2013, the International Initiative on Thrombosis and Cancer (ITAC-CME) released international guidelines for the treatment and prophylaxis of VTE and central venous catheter-associated thrombosis, based on a systematic review of the literature ranked according to the Grading of Recommendations Assessment, Development, and Evaluation scale. An update of these ITAC-CME consensus guidelines, including the use of direct oral anticoagulants, was recently published. In this review, we summarize these updated guidelines. Better adherence to the international guidelines, involving an adequate educational and active implementation strategies, will substantially decrease the burden of VTE and allow to increase survival in cancer patients.

Introduction: International clinical practice guidelines (ITAC, ASCO, NCCN and ASH) have progressively endorsed direct factor Xa inhibitors (edoxaban, rivaroxaban and apixaban) as an alternative to monotherapy with low-molecular-weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) in cancer patients. The results from new randomized controlled trials (RCT) which assessed the efficacy and the safety of direct oral anticoagulants (DOAC) compared to LMWH for the treatment of cancer-associated thrombosis (CAT) were released during the past months. We therefore performed an updated meta-analysis of all publicly available data from RCT comparing DOAC with LMWH for the treatment of CAT. Methods: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and conference proceedings from all languages were searched up to August 2, 2021. Search strategy, study selection, data extraction and statistical analysis were performed in accordance with the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Risk of bias was assessed by using the Cochrane risk-of-bias tool in randomized controlled trials version 2.0. Pooled relative risk (RR) and 95% confidence intervals (CIs) were estimated using the Mantel-Haenszel method of Der Simonian and Laird within a random-effect model. Heterogeneity of effect size across studies was assessed using the I 2 statistic. Publication bias was assessed by visual inspection of funnel plots. All the statistical analyses were performed with the RevMan 5.3 software. Results: Six RCT comparing the efficacy and safety of DOAC versus LMWH, which enrolled a total of 3,690 cancer patients with acute VTE (1850 randomized to the DOAC arms and 1840 randomized to the LMWH arms), were included in the pooled analysis. Main study characteristics are summarized in Table 1. During a follow-up of 3 to 6 months under anticoagulant treatment, recurrent VTE occurred in 99 of 1,850 (5.3%) patients receiving DOACs versus 152 of 1,840 (8.3%) patients receiving LMWH. The risk of recurrent VTE was significantly lower with DOAC than with LMWH (RR 0.67, 95% CI 0.52-0.85, p = 0.001, I 2 = 0%, Figure 1A). Major bleeding occurred in 78 (4.2%) patients with CAT treated with DOAC versus 65 (3.5%) patients treated with LMWH. The risk of major bleeding was non significantly higher with DOAC (RR 1.20, 95% CI 0.85-1.70, p = 0.31, I 2= 7%, Figure 1B). CRNMB was more frequent in cancer patients receiving DOAC compared to those receiving LMWH (10.3% versus 6.3%, RR 1.63, 95% CI 1.25-2.11, p = 0.0003, I²= 6%, Figure 1C). The rates of all-cause mortality did not differ between the two groups (23.6% in the DOAC arms versus 23.3% in the LMWH arms, RR 1.02, 95% CI 0.89-1.16, p = 0.80, I² = 13%, Figure 1D). Conclusions: In this August 2021 meta-analysis of 3,690 patients treated for CAT, DOAC significantly reduced the risk of recurrent VTE compared with LMWH, without increasing the risk of major bleeding. However, as previously highlighted, the use of DOAC was associated with an increased risk of CRNMB. Our results provide additional evidence for the use of DOAC as a safe and effective first-line option for the treatment of CAT in patients who are not at high risk of bleeding. These findings may increase the level of certainty for the evidence used in the national or international clinical practice guidelines supporting the use of DOAC in cancer patients with CAT. Figure 1 Figure 1. Disclosures Connors: CSL Behring: Research Funding; Pfizer: Honoraria; Alnylam: Consultancy; takeda: Honoraria; Bristol-Myers Squibb: Honoraria; Abbott: Consultancy.

Objectifs Notre equipe a developpe une plateforme multidisciplinaire proactive « Allo-Thrombose Cancer » (Allo-TC) dediee a la prise en charge individualisee de la maladie thromboembolique veineuse (MTEV) chez les patients atteints de cancer, incluant un programme d’education therapeutique et un suivi personnalise. Elle vise a coordonner le parcours de soins patient, a ameliorer l’observance therapeutique, l’autonomisation, le confort psychologique et la qualite de vie. L’objectif de cette etude etait d’evaluer l’efficience de cette plateforme. Methodes Entre septembre 2017 et octobre 2019, nous avons realise une etude monocentrique, prospective, en soins courants, interventionnelle, comparant la prise en charge habituelle de la MTEV dans une cohorte historique de 50 patients avec cancer et MTEV a celle de 50 patients avec cancer et MTEV consecutivement inclus dans le programme Allo-TC. Le critere d’evaluation principal etait le taux d’adhesion aux recommandations internationales ITAC de bonne pratique clinique (BPC) pour le traitement de la MTEV associee au cancer, evalue a 6 mois de suivi. Resultats Les localisations primitives du cancer etaient principalement genito-urinaire (22 %), mammaire (19 %), gastro-intestinale (16 %), hematologique (lymphomes, 15 %), et pulmonaire (11 %). Cinquante et un patients (61 %) presentaient un cancer metastatique a l’inclusion. Les caracteristiques cliniques des patients ne differaient pas entre les 2 cohortes a l’inclusion. Les taux de patients recevant un traitement anticoagulant conforme aux recommandations internationales de BPC evalues a l’inclusion, puis a 3 et 6 mois de suivi ont ete de 84 %, 8 % et 16 %, respectivement, dans la cohorte historique, versus 100 %, 72 % et 68 %, respectivement, dans la cohorte Allo-TC (p Conclusion Le programme Allo-TC permet d’ameliorer significativement la prise en charge de la MTEV chez les patients atteints de cancer.

Les recommandations internationales ITAC pour la prise en charge de la maladie thromboembolique veineuse (MTEV) chez les patients atteints de cancer ont ete remises a jour et publiees en septembre 2019 (Farge D., Frere C., et al. Lancet Oncol. 2019). Leur publication s’accompagne de la mise a jour d’une application pour smartphone dediee, visant a guider le clinicien dans ses prescriptions. Cette application est telechargeable gratuitement sur le site http://www.itac-cme.com/ , sur l’App Store et sur Google Play. Elle est disponible en versions anglaise et francaise. Il s’agit de la premiere application mobile visant a promouvoir une strategie therapeutique optimale pour le traitement curatif et prophylactique de la MTEV chez les patients atteints de cancer. Elle se fonde sur des algorithmes decisionnels clairs, bases sur les recommandations ITAC, et aborde les situations cliniques les plus frequemment rencontrees en pratique quotidienne : prophylaxie en milieu chirurgical, en milieu medical, en ambulatoire, traitement curatif des thromboses veineuses profondes des membres inferieurs, de l’embolie pulmonaire et des thromboses sur catheter central. Un menu d’accueil permet a l’utilisateur de choisir le contexte (prophylaxie primaire, traitement curatif d’une MTEV hors thrombose sur catheter central, traitement curatif d’une MTEV sur catheter central). Celui-ci est invite a repondre a un nombre limite de questions permettant de preciser la situation clinique et le profil du patient (traitement initial, d’entretien, a long terme ou d’une recidive sous traitement ; traitements en cours, contre-indications aux anticoagulants, clairance de la creatinine du patient). Une fois ces informations colligees, l’application indique quelle est la meilleure strategie therapeutique (choix de l’anticoagulant, schema posologique, duree du traitement). L’icone « information » permet de visualiser la synthese des donnees du patient. Le menu permet d’acceder a differents outils, dont une aide contextuelle, une synthese des recommandations internationales ITAC, les references bibliographiques princeps, et un forum de discussion. Cette application intuitive guide ainsi le clinicien dans le choix de la strategie therapeutique la mieux adaptee a la situation clinique a laquelle il est confronte, en tenant compte du profil individuel du patient, et lui fournit un acces simple et actualise aux recommandations ITAC 2019 pour la prise en charge de la MTEV chez les patients atteints de cancer.

Objectifs Les recommandations internationales (ITAC) 2019 pour la prise en charge de la maladie thromboembolique veineuse (MTEV) chez les patients atteints de cancer ont ete publiees dans le Lancet Oncology en septembre 2019. Materiel et methodes Elaborees par un groupe d’experts internationaux, en lien avec l’Institut national du cancer (INCa), selon une approche « Grading of Recommendations Assessment, Development and Evaluation » (GRADE), toutes les donnees de la litterature disponibles sur le traitement curatif et preventif de la MTEV en milieu medical et chirurgical chez les patients avec cancer de 1996 a 2019 ont ete analysees de facon exhaustive, incluant les resultats des derniers essais randomises controles ayant evalue l’efficacite et la securite des anticoagulants oraux directs (AOD). Resultats La methodologie et le manuscrit ont ete revus et valides par l’International Society of Thrombosis and Haemostasis (ISTH). Les nouveautes concernent l’utilisation des HBPM pour le traitement curatif et des AOD dans le traitement curatif et preventif de la MTEV au cours du cancer et seront presentees. Conclusion La publication de ces recommandations s’accompagne d’une mise a jour de l’application dediee, d’acces gratuit et telechargeable sur smartphone ( http://www.itaccme.org/ ).

International audience; Over the past two decades, aspirin has emerged as a promising chemoprotective agent to prevent colorectal cancer (CRC). In 2016, the mounting evidence supporting its chemoprotective effect, from both basic science and clinical research, led the US Preventive Services Task Force to recommend regular use of low-dose aspirin in some subgroups of patients for whom the benefits are deemed to outweigh the risks. In contrast, data on the chemoprotective effect of aspirin against other cancers are less clear and remain controversial. Most data come from secondary analyses of cardiovascular prevention trials, with only a limited number reporting cancer outcomes as a prespecified endpoint, and overall unclear findings. Moreover, the potential chemoprotective effect of aspirin against other cancers has been recently questioned with the publication of 3 long-awaited trials of aspirin in the primary prevention of cardiovascular diseases reporting no benefit of aspirin on overall cancer incidence and cancer-related mortality. Data on the chemoprotective effects of other antiplatelet agents remain scarce and inconclusive, and further research to examine their benefit are warranted. In this narrative review, we summarize current clinical evidence and continuing controversies on the potential chemoprotective properties of antiplatelet agents against cancer.

International audience; Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

International audience; BackgroundTicagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared with clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, data regarding PR from ticagrelor and the outcomes are lacking.MethodsThis study aimed to determine the association between PR after a ticagrelor loading dose (LD), assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention. The authors performed a prospective, multicenter observational study on patients treated with percutaneous coronary intervention for ACS. The VASP index was used to assess PR after ticagrelor LD. The primary endpoint was the link between major adverse cardiac events (MACE) and PR.ResultsAmong the included 530 patients with ACS, 185 (34.5%) were admitted for ST-segment elevation myocardial infarction. This study observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1 ± 16.6%). At 1 month, 21 MACE (3.8%) and 29 Academic Research Consortium ≥2 bleeding events (5.5%) were recorded. Neither MACE nor bleeding were associated with PR (p = 0.34 and p = 0.78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (p = 0.03). PR was the only factor associated with acute definite stent thrombosis.ConclusionIn patients receiving a ticagrelor LD while undergoing percutaneous coronary intervention for ACS, PR using the VASP does not predict MACE or bleeding at 1 month, but it is significantly associated with the occurrence of definite acute ST.

International audience; BACKGROUND:Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome.OBJECTIVES:We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI).METHODS:We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR.RESULTS:Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis.CONCLUSION:In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.

International audience; Venous thromboembolism (VTE) is a major common complication in cancer patients. Risk-adapted thromboprophylaxis and antithrombotic therapy for patients diagnosed with VTE can reduce the recurrence of VTE events. Thrombotic risk varies according to cancer type, stage, and comorbidities. The current review analyzes most recent data and provides clinical guidance for the management of women with cancer-associated thrombosis.

International audience; Background & aims: Pancreatic ductal adenocarcinoma (PDAC) is associated with the highest incidence of venous thromboembolism (VTE) of any cancer type. However, little is known about risk factors for VTE or its outcomes in patients with PDAC.Methods: We collected data from a prospective, observational study performed at multiple centers in France from May 2014 through November 2018 (the Base Clinico-Biologique de l'Adénocarcinome Pancréatique [BACAP] study) linked to a database of patients with a new diagnosis of PDAC of any stage. Data were collected from 731 patients at baseline and during clinical follow-up or in the event of symptoms. The primary endpoint was the onset of VTE during follow-up. The secondary endpoints were progression-free survival (PFS) and overall survival (OS) times.Results: During a median follow-up of 19.3 months, 152 patients (20.79%) developed a VTE. The median time from PDAC diagnosis to the onset of VTE was 4.49 months. Cumulative incidence values of VTE were 8.07% (95% confidence interval [CI], 6.31-10.29) at 3 months and 19.21% (95% CI, 16.27-22.62) at 12 months. In multivariate analysis, PDAC primary tumor location (isthmus vs head: hazard ratio [HR], 2.06; 95% CI, 1.09-3.91; P = .027) and stage (locally advanced vs resectable or borderline: HR, 1.66; 95% CI, 1.10-2.51, P = .016; metastatic vs resectable or borderline: HR, 2.50; 95% CI, 1.64-3.79; P < .001) were independent risk factors for the onset of VTE. Patients who developed VTE during follow-up had shorter times of PFS (HR, 1.74; 95% CI, 1.19-2.54; P = .004) and OS (HR, 2.02; 95% CI, 1.57-2.60; P < .001).Conclusion: In an analysis of data from the BACAP study, we found that frequent and early onsets of VTE after diagnoses of PDAC are associated with significant decreases in times of PFS and OS. Studies are needed to determine whether primary prophylaxis of VTE in patients with PDAC will improve morbidity and mortality related to VTE. (ClinicalTrials.gov, Number: clinicaltrials.gov as number NCT02818829).

Venous thromboembolism (VTE) is a common complication in patients with cancer and is associated with poor prognosis. Low-molecular-weight heparins (LMWHs) are the standard of care for the treatment of cancer-associated thrombosis. Primary VTE prophylaxis with LMWH is recommended after cancer surgery and in hospitalized patients with reduced mobility. However, owing to wide variations in VTE and bleeding risk, based on disease stage, anti-cancer treatments, and individual patient characteristics, routine primary prophylaxis is not recommended in ambulatory cancer patients undergoing chemotherapy. Efforts are under way to validate risk assessment models that will help identify those patients in whom the benefits of primary prophylaxis will outweigh the risks. In recent months, long-awaited dedicated clinical trials assessing the direct oral anticoagulants (DOACs) in patients with cancer have reported promising results. In comparison with the LMWHs, the DOACs were reported to be non-inferior to prevent VTE recurrence. However, there was an increased risk of bleeding, particularly in gastrointestinal cancers. Safe and optimal treatment with the DOACs in the patient with cancer will require vigilant patient selection based on patient characteristics, co-morbidities, and the potential for drug–drug interactions.

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