Author: "Corinne Frere" / Topic: business - Searchworks@Jio Institute Digital Library Search Results

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1. Hemostasis testing in patients with liver dysfunction: Advantages and caveats

Author: B. Crichi, Manon Lejeune, Guillaume Nguyen, Corinne Frere, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service de Médecine Interne [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-SU, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Thrombin generation, medicine.medical_specialty, Hemostatic agents, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Bleeding risk, Internal medicine, medicine, Humans, In patient, Conventional tests, Hemostasis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Viscoelastic tests, business.industry, Liver Diseases, Minireviews, General Medicine, Blood Coagulation Disorders, Thrombelastography, 3. Good health, 030211 gastroenterology & hepatology, Blood Coagulation Tests, Liver dysfunction, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: 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.
Published: 2021

2. Incidence, risk factors, and management of bleeding in patients receiving anticoagulants for the treatment of cancer-associated thrombosis

Author: Nicolas Janus, B. Crichi, Corinne Frere, Philippe Girard, Carme Font, and F. Esposito
Subjects: medicine.medical_specialty, Anemia, medicine.drug_class, Population, Low molecular weight heparin, Hemorrhage, law.invention, Randomized controlled trial, Risk Factors, law, Neoplasms, medicine, Humans, Adverse effect, Intensive care medicine, education, education.field_of_study, business.industry, Incidence, Anticoagulant, Anticoagulants, Thrombosis, Venous Thromboembolism, Heparin, Low-Molecular-Weight, medicine.disease, Oncology, Risk assessment, business
Abstract: 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.
Published: 2021

3. Patient education program at the forefront of cancer-associated thrombosis care

Author: I. Madeleine, L. Deville, O. Bensaoula, C. Bonnet, A. Ndour, M. Sebuhyan, C. Le Maignan, B. Crichi, Dominique Farge, J. Rueda, Zora Marjanovic, and Corinne Frere
Subjects: medicine.medical_specialty, business.industry, medicine.drug_class, education, Anticoagulant, Cancer, Thrombosis, Disease, Heparin, Low-Molecular-Weight, medicine.disease, Patient Education as Topic, Quality of life, Neoplasms, Internal medicine, Quality of Life, medicine, Humans, Cancer associated thrombosis, Quality of care, Cardiology and Cardiovascular Medicine, business, Retrospective Studies, Patient education
Abstract: 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.
Published: 2021

4. Extracorporeal Membrane Oxygenation Induces Early Alterations in Coagulation and Fibrinolysis Profiles in COVID-19 Patients with Acute Respiratory Distress Syndrome

Author: Guillaume Lebreton, Ania Nieszkowska, Corinne Frere, Marc Pineton de Chambrun, Isabelle Martin-Toutain, Guillaume Hékimian, Manon Lejeune, Paul Masi, Juliette Chommeloux, Matthieu Schmidt, Charles-Edouard Luyt, Alain Combes, Nicolas Bréchot, Cyrielle Desnos, and Pascal Leprince
Subjects: Adult, Male, ARDS, medicine.medical_specialty, medicine.medical_treatment, Hemorrhage, 030204 cardiovascular system & hematology, Fibrinogen, law.invention, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Von Willebrand factor, law, Internal medicine, von Willebrand Factor, Fibrinolysis, medicine, Extracorporeal membrane oxygenation, Humans, Prospective Studies, Blood Coagulation, Respiratory Distress Syndrome, biology, business.industry, COVID-19, 030208 emergency & critical care medicine, Hematology, Middle Aged, medicine.disease, Intensive care unit, Coagulation, biology.protein, Cardiology, Female, Median body, business, medicine.drug
Abstract: 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
Published: 2021

5. Comparaison des caractéristiques et des pronostics des patients avec et sans cancer actif hospitalisés pour une infection à SARS-CoV-2

Author: Alexandre Le Joncour, Joe-Elie Salem, Pierre Salem, Olivier Benveniste, Charlotte Fenioux, Corinne Frere, Yves Allenbach, David Saadoun, Christian Funck-Brentano, Joseph Gligorov, Patrice Cacoub, Aurore Vozy, Matheus Vieira, Luca Campedel, Paul Gougis, and Georgina Maalouf
Subjects: Male, 0301 basic medicine, Paris, Cancer Research, medicine.medical_specialty, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, Article Original, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Intensive care, Internal medicine, Pandemic, medicine, Humans, Cardiovascular complications, Radiology, Nuclear Medicine and imaging, Prospective Studies, education, Prospective cohort study, Pandemics, Complications cardio-vasculaires, Aged, Cancer, Aged, 80 and over, Cross Infection, education.field_of_study, business.industry, COVID-19, Hematology, General Medicine, Middle Aged, medicine.disease, Thrombosis, Hospitalization, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Female, business, Cohort study
Abstract: 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.
Published: 2021

6. Letter to the editors-in-chief reply to: Solinas et al. Venous and arterial thromboembolic events with immune check point inhibitors: A systematic review

Author: Joe-Elie Salem, Stéphane Ederhy, and Corinne Frere
Subjects: Immune system, business.industry, Immune checkpoint inhibitors, Medicine, Hematology, business, Bioinformatics, Check point, Venous thromboembolism
Published: 2021

7. An epidemic of redundant meta‐analyses

Author: Céline Chapelle, Edouard Ollier, Philippe Girard, Michel Cucherat, Patrick Mismetti, Silvy Laporte, and Corinne Frere
Subjects: medicine.medical_specialty, business.industry, Hematology, 030204 cardiovascular system & hematology, Original research, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Meta-analysis, medicine, Forest plot, Treatment effect, medicine.symptom, Intensive care medicine, business, Venous thromboembolism, Major bleeding, Confusion
Abstract: 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.
Published: 2021

8. Acquired factor V inhibitor: a nation‐wide study of 38 patients

Author: Nadine Ajzenberg, Elodie Rabut, Nicolas Schleinitz, Annabelle Dupont, Thomas Papo, Dorothée Faille, Tiphaine Goulenok, Emmanuelle de Raucourt, Chloé James, Karim Sacre, Corinne Frere, Claire Vasco, and Lucia Rugeri
Subjects: Adult, Male, Risk, Severe bleeding, medicine.medical_specialty, Hemorrhage, Comorbidity, Factor V inhibitor, Cross Reactions, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Isoantibodies, Internal medicine, medicine, Humans, In patient, Aged, Autoantibodies, Retrospective Studies, Aged, 80 and over, Prothrombin time, biology, medicine.diagnostic_test, business.industry, Factor V, Immunoglobulins, Intravenous, Retrospective cohort study, Hematology, Middle Aged, Anti-Bacterial Agents, Immunoglobulin G, 030220 oncology & carcinogenesis, Prothrombin Time, biology.protein, Female, France, business, Immunosuppressive Agents, Follow-Up Studies, 030215 immunology
Abstract: 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.
Published: 2021

9. Heparin-induced thrombocytopenia in COVID-19 patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation: two case reports

Author: Guillaume Hékimian, Guillaume Lebreton, Corinne Frere, Alain Combes, Isabelle Martin-Toutain, Frank Bidar, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, ARDS, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 0206 medical engineering, Biomedical Engineering, Medicine (miscellaneous), 02 engineering and technology, 030204 cardiovascular system & hematology, Argatroban, law.invention, Biomaterials, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, law, Heparin-induced thrombocytopenia, Coagulopathy, Extracorporeal membrane oxygenation, Humans, Medicine, Intensive care medicine, Respiratory Distress Syndrome, Heparin, business.industry, Anticoagulants, COVID-19, Middle Aged, medicine.disease, Thrombocytopenia, 020601 biomedical engineering, Intensive care unit, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, surgical procedures, operative, Female, Cardiology and Cardiovascular Medicine, business, Complication, medicine.drug
Abstract: 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.
Published: 2020

10. Systemic Inflammatory Response Syndrome Is a Major Contributor to COVID-19–Associated Coagulopathy

Author: Isabelle Martin-Toutain, Juliette Chommeloux, Alain Combes, Nicolas Bréchot, Charles Edouard Luyt, Ania Nieszkowska, Corinne Frere, Matthieu Schmidt, Guillaume Hékimian, Guillaume Lebreton, Marc Pineton de Chambrun, Cyrielle Desnos, Manon Lejeune, and Paul Masi
Subjects: medicine.medical_specialty, biology, Coronavirus disease 2019 (COVID-19), business.industry, 030204 cardiovascular system & hematology, biology.organism_classification, Single Center, medicine.disease, Systemic inflammatory response syndrome, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, Pandemic, medicine, Coagulopathy, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, Prospective cohort study, business, Betacoronavirus, Cohort study
Published: 2020

11. Response to Letter: ‘Reply to 'High frequency of antiphospholipid antibodies in critically ill COVID‐19 patients: a link with hypercoagulability?'’

Author: Corinne Frere, A. Mathian, Guillaume Hékimian, Makoto Miyara, M. Pineton De Chambrun, Isabelle Martin-Toutain, Z. Amoura, and Alain Combes
Subjects: 0301 basic medicine, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Critical Illness, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, 030204 cardiovascular system & hematology, Virus diseases, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, Humans, Thrombophilia, Medicine, In patient, Intensive care medicine, biology, SARS-CoV-2, business.industry, Critically ill, COVID-19, 030104 developmental biology, Antibodies, Antiphospholipid, biology.protein, Antibody, business
Abstract: 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.
Published: 2020

12. High frequency of antiphospholipid antibodies in critically ill COVID‐19 patients: a link with hypercoagulability?

Author: Guillaume Hékimian, Z. Amoura, A. Mathian, Makoto Miyara, M. Pineton De Chambrun, Corinne Frere, Isabelle Martin-Toutain, and Alain Combes
Subjects: 0301 basic medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), macromolecular substances, 030204 cardiovascular system & hematology, Fibrinogen, Systemic inflammation, Gastroenterology, SARS‐CoV‐2, 03 medical and health sciences, 0302 clinical medicine, COVID‐19, Internal medicine, antiphospholipid antibody, Internal Medicine, medicine, Letters to the Editor, Letter to the Editor, thrombosis, medicine.diagnostic_test, biology, business.industry, Retrospective cohort study, medicine.disease, Pulmonary embolism, Pneumonia, 030104 developmental biology, biology.protein, medicine.symptom, Antibody, business, medicine.drug, Partial thromboplastin time
Abstract: 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.
Published: 2020

13. Primary prophylaxis of venous thromboembolism in extragonadal germ-cell tumour

Author: P. Kubicek, E. Boughalem, and Corinne Frere
Subjects: Oncology, medicine.medical_specialty, Extragonadal, business.industry, Treatment outcome, MEDLINE, Internal medicine, Primary prevention, medicine, Cardiology and Cardiovascular Medicine, Risk assessment, business, Venous thromboembolism, Germ cell tumour
Published: 2020

14. On-ticagrelor platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention for acute coronary syndrome

Author: Bernard Jouve, Thomas Cuisset, Marie-Christine Alessi, Gilles Lemesle, Corinne Frere, Vassili Panagides, Franck Paganelli, Julien Mancini, Marc Laine, Caroline Gouarne, Laurent Bonello, Service de cardiologie [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hopital d'Aix en Provence, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, platelet reactivity, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, VASP index, 0302 clinical medicine, Medicine, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Stroke, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Microfilament Proteins, Hematology, Middle Aged, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], Treatment Outcome, Cardiology, Female, Ticagrelor, medicine.drug, Blood Platelets, Acute coronary syndrome, medicine.medical_specialty, Platelet Function Tests, Hemorrhage, ticagrelor, acute coronary syndrome, 03 medical and health sciences, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Humans, cardiovascular diseases, Aged, business.industry, Surrogate endpoint, Percutaneous coronary intervention, Phosphoproteins, Platelet Activation, medicine.disease, ADP receptor inhibitor, Conventional PCI, Purinergic P2Y Receptor Antagonists, ST Elevation Myocardial Infarction, business, Cell Adhesion Molecules, Platelet Aggregation Inhibitors, Mace, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: 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.
Published: 2021

15. Endothelial cell biomarkers in critically ill COVID‐19‐patients with encephalitis

Author: Joe-Elie Salem, Sandrine Bourdoulous, Loïc Le Guennec, Sophie Demeret, Clémence Marois, Benjamin Rohaut, Jason Ziveri, Corinne Frere, Albert Cao, Victor Altmayer, Nicolas Weiss, Institut de neurosciences translationnelles de Paris (NeurATRIS - IHU-A-ICM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Paris Est, REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aigüE [CHU Pitié-Salpêtrière] (GRC RESPIRE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), [Institut Cochin] Departement Infection, immunité, inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Bourdoulous, Sandrine
Subjects: medicine.medical_specialty, Critical Illness, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Angiopoietinlike-4, Thrombomodulin, Systemic inflammation, Biochemistry, Gastroenterology, law.invention, Endothelial activation, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Angiopoietin-Like Protein 4, Humans, Endothelial dysfunction, Pathological, Endothelial cell biomarker, 030304 developmental biology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Tumor Necrosis Factor-alpha, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Endothelial Cells, COVID-19, acute respiratory distress syndrome, medicine.disease, Intensive care unit, 3. Good health, Intensive Care Units, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Encephalitis, medicine.symptom, Complication, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: 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
Published: 2021

16. How to screen and diagnose deep venous thrombosis (DVT) in patients hospitalized for or suspected of COVID-19 infection, outside the intensive care units

Author: A Bergeron-Lafaurie, O. Peyrony, M. Sebuhyan, B. Crichi, B Denis, R Mirailles, Corinne Frere, G Liegeon, P Bonnin, Dominique Farge, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, Deep vein, [SDV]Life Sciences [q-bio], Clinical Decision-Making, COVID-19 pandemic, Context (language use), Review, 030204 cardiovascular system & hematology, Asymptomatic, Doppler ultrasound, law.invention, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, 0302 clinical medicine, Four-points compression ultrasound, law, Predictive Value of Tests, Risk Factors, Intensive care, medicine, COVID-19 associated coagulopathy, Humans, 030212 general & internal medicine, cardiovascular diseases, Wells score, Venous Thrombosis, business.industry, Incidence, Pulmonary embolism, COVID-19, Ultrasonography, Doppler, medicine.disease, Intensive care unit, Thrombosis, 3. Good health, Hospitalization, Venous thrombosis, medicine.anatomical_structure, Emergency medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers, Venous thromboembolism
Abstract: 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.
Published: 2020

17. Overcoming bleeding events related to extracorporeal membrane oxygenation in COVID-19 – Authors' reply

Author: Alain Combes, Guillaume Hekimian, Matthieu Schmidt, Corinne Frere, Juliette Chommeloux, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Pandemic, Correspondence, Extracorporeal membrane oxygenation, Medicine, 030212 general & internal medicine, business, Intensive care medicine, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

18. Management of Cancer-Associated Thrombosis: An Evolving Area

Author: Jean M. Connors, Dominique Farge, Corinne Frere, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche clinique appliquée à l'hématologie (URP_3518), Université de Paris (UP), McGill University = Université McGill [Montréal, Canada], Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Paris Cité (UPCité)
Subjects: Cancer Research, medicine.medical_specialty, Side effect, medicine.drug_class, low-molecular weight heparin, [SDV]Life Sciences [q-bio], venous thromboembolism, Low molecular weight heparin, direct oral anticoagulant, 030204 cardiovascular system & hematology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, medicine, Cancer associated thrombosis, cancer, Intensive care medicine, business.industry, Cancer, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Thrombosis, risk assessment model, 3. Good health, [SDV] Life Sciences [q-bio], Editorial, Clinical research, Oncology, 030220 oncology & carcinogenesis, business, Venous thromboembolism
Abstract: 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.
Published: 2020

19. Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis

Author: Jean M. Connors, Dominique Farge, Corinne Frere, Guillaume Hékimian, M. Sakka, I. Colmegna, B. Crichi, D. Bonnefont-Rousselot, I. Martin-Toutain, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), McGill University = Université McGill [Montréal, Canada], Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and CCSD, Accord Elsevier
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Pneumonia, Viral, 030204 cardiovascular system & hematology, Risk Assessment, Severity of Illness Index, Article, Fibrin Fibrinogen Degradation Products, D-Dimer, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Internal medicine, Severity of illness, Risk of mortality, medicine, Humans, 030212 general & internal medicine, Mortality, Pandemics, Survival analysis, IQR, interquartile range, Retrospective Studies, Coronavirus disease 2019, business.industry, SARS-CoV-2, ADRS, acute detress respiratory syndrome, COVID-19, Retrospective cohort study, Middle Aged, Survival Analysis, Confidence interval, 3. Good health, NR, not reported, Hospitalization, [SDV] Life Sciences [q-bio], Strictly standardized mean difference, COVID-19, Coronavirus Disease 2019, biomarker, Observational study, Female, Risk assessment, business, Coronavirus Infections, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract: 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
Published: 2020
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20. Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Author: Louis Buscail, Dominique Farge, Nassim Ait Abdallah, Barbara Bournet, B. Crichi, Corinne Frere, Cindy Canivet, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Recherche clinique appliquée à l'hématologie (URP_3518), Université de Paris (UP), McGill University = Université McGill [Montréal, Canada], Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and Université Paris Cité (UPCité)
Subjects: Cancer Research, medicine.medical_specialty, anticoagulants, medicine.drug_class, pancreatic cancer, venous thromboembolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, chemotherapy, lcsh:RC254-282, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, [SDV.CAN] Life Sciences [q-bio]/Cancer, law, Internal medicine, medicine, business.industry, Anticoagulant, Absolute risk reduction, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Confidence interval, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Oncology, major bleeding, 030220 oncology & carcinogenesis, Relative risk, Meta-analysis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Ambulatory, Number needed to treat, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, thromboprophylaxis, business
Abstract: 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.
Published: 2020

21. Tissue damage from neutrophil-induced oxidative stress in COVID-19

Author: Philippe Nuss, Carole Elbim, Chrystel Becker, Mireille Laforge, Corinne Frere, Charbel Massaad, Jean-Jacques Benoliel, Miryana Hémadi, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS (UMR_7086)), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de psychiatrie adulte [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Laforge, Mireille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Psychiatrie adultes [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Service de Biochimie Endocrinienne et Oncologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP]
Subjects: 0301 basic medicine, History, Neutrophils, [SDV]Life Sciences [q-bio], medicine.disease_cause, Extracellular Traps, Severity of Illness Index, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Antioxidants, Acetylcysteine, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lymphocytes, Lung, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Sulfonamides, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, NF-kappa B, Thrombosis, 3. Good health, Computer Science Applications, medicine.anatomical_structure, Fuel Technology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Host-Pathogen Interactions, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, Drug Therapy, Combination, Coronavirus Infections, medicine.drug, NF-E2-Related Factor 2, Pneumonia, Viral, Glycine, Proteinase Inhibitory Proteins, Secretory, Energy Engineering and Power Technology, Education, Superoxide dismutase, 03 medical and health sciences, Betacoronavirus, medicine, Humans, Neutrophil to lymphocyte ratio, Author Correction, Pandemics, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Reactive oxygen species, business.industry, SARS-CoV-2, Superoxide Dismutase, COVID-19, NFKB1, medicine.disease, Immunity, Innate, Red blood cell, Oxidative Stress, 030104 developmental biology, chemistry, Gene Expression Regulation, Immunology, biology.protein, business, Reactive Oxygen Species, Oxidative stress, 030215 immunology
Abstract: 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.
Published: 2020
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22. Reduced Rivaroxaban Dose Versus Dual Antiplatelet Therapy After Left Atrial Appendage Closure: ADRIFT a Randomized Pilot Study

Author: Nicolas Lellouche, Marie Hauguel-Moreau, Didier Klug, Hui Wang, Jean-Michel Juliard, Guillaume Duthoit, Isabelle Martin-Toutain, Eric Vicaut, N. Zannad, Delphine Brugier, Corinne Frere, Jacques Mansourati, Sandrine Deltour, Gregory Ducrocq, Solohaja-Faniaha Dimby, Eric Brochet, Eloi Marijon, Nassim Braik, Luc Lorgis, Nadjib Hammoudi, Johanne Silvain, Christian Spaulding, Batric Popovic, Antoine Lepillier, David Attias, Gilles Montalescot, and Alexandre Ceccaldi
Subjects: Male, medicine.medical_specialty, Cardiac Catheterization, Percutaneous, Time Factors, Antithrombin III, Atrial Appendage, Pilot Projects, 030204 cardiovascular system & hematology, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Rivaroxaban, Left atrial, Heart Rate, Internal medicine, Atrial Fibrillation, Medicine, Humans, 030212 general & internal medicine, Contraindication, Blood Coagulation, Aged, Appendage, Aged, 80 and over, business.industry, Dual Anti-Platelet Therapy, Atrial fibrillation, Thrombosis, Clopidogrel, medicine.disease, Peptide Fragments, 3. Good health, Treatment Outcome, Cardiology, Atrial Function, Left, Female, Prothrombin, France, Cardiology and Cardiovascular Medicine, business, Biomarkers, Platelet Aggregation Inhibitors, medicine.drug, Factor Xa Inhibitors, Peptide Hydrolases
Abstract: 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.
Published: 2020

23. Are Patients with Active Cancer and Those with History of Cancer Carrying the Same Risks of Recurrent VTE and Bleeding While on Anticoagulants?

Author: Manon Lejeune, Corinne Frere, Jean-Philippe Spano, B. Crichi, Nicolas Janus, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Cancer Research, medicine.medical_specialty, medicine.drug_class, Population, MEDLINE, Subgroup analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, active cancer, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, history of cancer, cancer-associated-thrombosis, education, Prospective cohort study, education.field_of_study, business.industry, Anticoagulant, anticoagulant, Cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Thrombosis, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Cohort, Perspective, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract: 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.
Published: 2020

24. Primary Thromboprophylaxis in Pancreatic Cancer Patients: Why Clinical Practice Guidelines Should Be Implemented

Author: Dominique Farge, Mehdi Ouaissi, Janusz Rak, George Zogoulous, Eric Vicaut, Jefferey Barkun, Barbara Bournet, Thierry Conroy, Louis Buscail, Corinne Frere, Recherche clinique appliquée à l'hématologie (URP_3518), Université de Paris (UP), Service de Médecine Interne [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), McGill University = Université McGill [Montréal, Canada], Université Fédérale Toulouse Midi-Pyrénées, CHU Toulouse [Toulouse], Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, AP-HP, GH Saint-Louis – Lariboisière – F. Widal, Département de biostatistiques et d'informatique médicales, Paris, France, McGill University Health Center [Montreal] (MUHC), Departement d'Hépato-Gastroentérologie et Cancérologie Digestive [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vialaron, Sylvie, Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Cancer Research, medicine.medical_specialty, low-molecular weight heparin, venous thromboembolism, pancreatic cancer, Context (language use), Subgroup analysis, direct oral anticoagulant, Review, 030204 cardiovascular system & hematology, Malignancy, lcsh:RC254-282, survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Randomized controlled trial, law, Pancreatic cancer, Medicine, Intensive care medicine, business.industry, Cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, thromboprophylaxis, business, Risk assessment
Abstract: 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.
Published: 2020

25. Author Correction: Tissue damage from neutrophil-induced oxidative stress in COVID-19

Author: Charbel Massaad, Mireille Laforge, Miryana Hémadi, Jean Jacques Benoliel, Corinne Frere, Carole Elbim, Philippe Nuss, Chrystel Becker, Gestionnaire, Hal Sorbonne Université, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS (UMR_7086)), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Psychiatrie adultes [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de psychiatrie adulte [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP]
Subjects: 0303 health sciences, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), 030306 microbiology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Comment, Energy Engineering and Power Technology, Predictive markers, medicine.disease_cause, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Fuel Technology, Viral infection, Immunology, Tissue damage, Medicine, business, Oxidative stress, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: 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.
Published: 2020

26. Traitement curatif de la maladie thromboembolique veineuse chez les patients atteints de cancer : quelle place pour les anticoagulants oraux directs en 2018 ?

Author: Corinne Frere and Dominique Farge
Subjects: medicine.medical_specialty, education.field_of_study, medicine.drug_class, business.industry, Population, Low molecular weight heparin, Cancer, Retrospective cohort study, 030204 cardiovascular system & hematology, medicine.disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Health care, medicine, 030212 general & internal medicine, Risks and benefits, Claims database, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, education
Abstract: 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.
Published: 2018

27. Maladie thromboembolique veineuse et cancer du pancréas

Author: M Jamelot, Corinne Frere, Philippe Debourdeau, L. Buscail, I. Benzidia, A. Hij, B Bournet, Dominique Farge, Groupe francophone thrombose et cancer, and H. Rafii-Elayoubi
Subjects: medicine.medical_specialty, business.industry, Incidence (epidemiology), Cancer, 030204 cardiovascular system & hematology, medicine.disease, Malignancy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, Relative risk, Pancreatic cancer, Epidemiology, medicine, Adjuvant therapy, Cardiology and Cardiovascular Medicine, business
Abstract: 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
Published: 2018

28. Lean body weight is the best scale for venous thromboprophylaxis algorithm in severely obese patients undergoing bariatric surgery

Author: Stéphane Berdah, Thierry Bege, Anne Dutour, Corinne Frere, Sandrine Boullu, C. Vincentelli, Bénédicte Gaborit, Joe-Elie Salem, Pierre-Emmanuel Morange, Olivier Emungania, Pierre-Antoine Moulin, Assistance Publique - Hôpitaux de Marseille (APHM), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique-Hôpitaux de Marseille (AP-HM), Aix Marseille Université (AMU), Service de pharmacologie biologique [CHU Pitié-Salpâtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CIC Paris Est, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Sorbonne Université (SU), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service d'Hématologie clinique [CHU Pitié-Salpêtrière]
Subjects: Adult, Dalteparin, Male, medicine.medical_specialty, Multivariate analysis, Lean body weight, medicine.drug_class, [SDV]Life Sciences [q-bio], Ideal Body Weight, Bariatric Surgery, Low molecular weight heparin, Renal function, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Weight Loss, medicine, Humans, Mass index, Prospective Studies, Low-molecular-weight heparin, 2. Zero hunger, Pharmacology, Univariate analysis, business.industry, Body Weight, Anticoagulants, Venous Thromboembolism, Middle Aged, Anti-Xa activity, Obesity, Morbid, 3. Good health, Surgery, Regimen, Lean body mass, Female, Median body, Glomerular filtration rate, Severe obesity, business
Abstract: 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
Published: 2018

29. GFHT proposals on the practical use of argatroban — With specifics regarding vaccine-induced immune thrombotic thrombocytopaenia (VITT)

Author: Yannick Béjot, Anne Godier, B. Tardy, Isabelle Gouin-Thibault, Vincent Mémier, Guillaume Mourey, Virginie Siguret, Corinne Frere, Christine Mouton, Marie Toussaint-Hacquard, Philippe Nguyen, Bouhadjar Dahmani, Yves Gruel, Charlène Kuadjovi, Peggy Reiner, Céline Desconclois, Anne Bauters, Elodie Boissier, Alexandre Godon, Emmanuel de Maistre, Nadine Ajzenberg, Thomas Lecompte, Isabelle Crassard, Nathalie Hézard, Dominique Lasne, Georges Jourdi, Mathieu Laurichesse, Chloé James, Claire Flaujac, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), CHU Pessac, Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205] (Brain Tech Lab ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpitaux Universitaires de Genève (HUG), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Versailles, 78000 Le Chesnay, France, parent, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Trousseau [Tours], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Thrombocytopaenia, medicine.drug_class, [SDV]Life Sciences [q-bio], VITT, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Fibrinogen, Argatroban, 03 medical and health sciences, 0302 clinical medicine, Concomitant Therapy, medicine, Platelet, business.industry, Anticoagulant, COVID-19, Thrombosis, General Medicine, medicine.disease, 3. Good health, Anesthesiology and Pain Medicine, Clotting time, Direct thrombin inhibitor, 030220 oncology & carcinogenesis, Anesthesia, business, Vaccine, medicine.drug
Abstract: 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.
Published: 2021

30. Nouvelles recommandations internationales pour le traitement curatif et prophylactique de la maladie thromboembolique veineuse chez les patients atteints d’un cancer et application dédiée pour smartphone

Author: pour le Groupe Francophone Thrombose et Cancer, I. Benzidia, Corinne Frere, A Solanilla, M Jamelot, M K Nguessan, U Michon-Pasturel, A. Hij, Dominique Farge, J Connault, and C. Le Maignan
Subjects: medicine.medical_specialty, business.industry, education, Cancer, 030204 cardiovascular system & hematology, Smartphone application, medicine.disease, Thrombosis, 03 medical and health sciences, 0302 clinical medicine, Curative treatment, 030220 oncology & carcinogenesis, medicine, cardiovascular diseases, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, Complication, Venous thromboembolism, Major bleeding, Cause of death
Abstract: 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.
Published: 2017

31. Direct Oral Anticoagulant Versus Low Molecular Weight Heparin for the Treatment of Cancer-Associated Thromboembolism: 2021 Updated Meta-Analysis of Randomized Controlled Trials

Author: Dominique Farge, Jean M. Connors, Corinne Frere, Pedro Henrique Prata, and Deborah Schrag
Subjects: Oncology, medicine.medical_specialty, business.industry, medicine.drug_class, Immunology, Cancer, Low molecular weight heparin, Cell Biology, Hematology, medicine.disease, Biochemistry, law.invention, Randomized controlled trial, law, Meta-analysis, Internal medicine, medicine, Oral anticoagulant, business
Abstract: 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.
Published: 2021

32. Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies

Author: Corinne Frere, Manon Lejeune, Pierre Kubicek, Dorothée Faille, Zora Marjanovic, the Groupe Francophone Thrombose et Cancer, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Chemoprotective agent, Cancer Research, medicine.medical_specialty, Colorectal cancer, aspirin, [SDV]Life Sciences [q-bio], colorectal cancer, Review, antiplatelet drugs, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, medicine, chemoprevention, cancer, 030212 general & internal medicine, Intensive care medicine, Aspirin, Cancer prevention, business.industry, Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Lynch syndrome, 3. Good health, Clinical research, Oncology, 030220 oncology & carcinogenesis, thienopyridines, Chemoprotective, cancer-related mortality, adenoma, business, medicine.drug
Abstract: 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.
Published: 2019

33. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer

Author: Ali Shamseddine, Juan I. Arcelus, Isabel Bogalho, Jérôme Connault, Hans Stricker, Maral Koolian, Ali Bazarbachii, Susan Solymoss, Andre Roussin, Thierry André, Gerald A. Soff, Stéphane Villiers, Enrique Gallardo, Ingrid Pabinger, Michel Nguessan, Marc Philip Righini, Hanno Riess, Joseph Emmerich, Pantep Angchaisuksiri, Dorit Blickstein, Ajay K. Kakkar, Dialina Brilhante, Pedro Ruiz-Artacho, Kenneth A. Bauer, Hugo A. Clemente, Emmanuel Messas, Walter Ageno, Anthony Marayevas, Anna Falanga, Vanessa Pachon Olmos, José Antonio Rueda-Camino, Sanjith Saseedharan, Javier Trujillo-Santos, Alexander Makatsariya, Arlette Ndour, Toutou Toussaint, Vicky Tagalakis, Hanadi Rafii, Raymond S.M. Wong, Fernando Ajauro, Antonio Moreira, Henri Bounameaux, Russel D. Hull, Ellis Martin, Florian Posch, Isabelle Madelaine, Joydeep Chakbrabartty, Mark Blostein, Kamal R. Al-Aboudi, Patricia Casais, Thierry Alcindor, Mario Mandalà, Corinne Frere, Lai Heng Lee, Eric Assenat, Ahmet M. Demir, Christine Marosi, Carme Font, Cecilia Guillermo, Luis Meillon, Viktoria Bitsadze, Ana Pais, Luisa Lopes Dos Santos, Ludovic Doucet, Thomas Gary, Andrés Muñoz, Ali T. Taher, Luis Jara-Palomares, Norizaku Yamada, Takayuki Ikezoe, Matthias Preusser, Cécile Durant, Jamilya Khrizroeva, Zora Marjanovic, Barbara Bournet, James D. Douketis, Clemens Feistritzer, Remedios Otero-Candelera, Alok A. Khorana, Jean-Christophe Gris, I. Benzidia, Nigel S. Key, A. Hij, Ramón Lecumberri, Cynthia Rothschild, Duarte Henrique Machado, Manuel Monreal, Jan Beyer-Westendorf, Jean M. Connors, Florian Langer, Darko Antic, Gabriela Cesarman-Maus, Dominique Farge, Benjamin Brenner, Antoine F. Carpentier, Charles W. Francis, Howard A. Liebman, Cihan Ay, Service de Médecine Interne [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), McGill University = Université McGill [Montréal, Canada], Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Medizinische Universität Wien = Medical University of Vienna, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University College of London [London] (UCL), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'angiologie et d'hémostase (MR), Hôpital Universitaire de Genève, McMaster University [Hamilton, Ontario], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), McGill University, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Medical University of Vienna, Universidad Complutense de Madrid [Madrid] (UCM), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: medicine.medical_specialty, Vitamin K, Vena Cava Filters, [SDV]Life Sciences [q-bio], education, MEDLINE, 030204 cardiovascular system & hematology, Anticoagulants/administration & dosage/therapeutic use, Venous Thromboembolism/drug therapy/etiology/prevention & control, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Neoplasms/complications/surgery, Central Venous Catheters, Humans, Medicine, In patient, Vitamin K/antagonists & inhibitors, Factor Xa Inhibitors/therapeutic use, Intensive care medicine, Grading (tumors), Heparin, Low-Molecular-Weight/administration & dosage/therapeutic use, Cause of death, ddc:616, Central Venous Catheters/adverse effects, business.industry, Anticoagulants, Venous Thromboembolism, Heparin, Low-Molecular-Weight, medicine.disease, Thrombosis, 3. Good health, Clinical trial, Clinical Practice, Fondaparinux, Oncology, Fondaparinux/therapeutic use, 030220 oncology & carcinogenesis, business, Venous thromboembolism, Factor Xa Inhibitors
Abstract: 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.
Published: 2019

34. TCT-415 Platelet Reactivity Inhibition Following Ticagrelor Loading Dose in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome

Author: Franck Paganelli, Caroline Gouarne, Corinne Frere, Thomas Cuisset, Marie-Christine Alessi, Franck Thuny, Vassili Panagides, Laurent Bonello, Julien Mancini, Service de cardiologie [Hôpital Nord - APHM], Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], and HAL AMU, Administrateur
Subjects: medicine.medical_specialty, Acute coronary syndrome, business.industry, medicine.medical_treatment, Percutaneous coronary intervention, 030204 cardiovascular system & hematology, medicine.disease, Loading dose, 3. Good health, Platelet reactivity, 03 medical and health sciences, 0302 clinical medicine, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Internal medicine, Cardiology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Medicine, In patient, 030212 general & internal medicine, cardiovascular diseases, Cardiology and Cardiovascular Medicine, business, Ticagrelor, medicine.drug
Abstract: 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.
Published: 2019

35. Platelet reactivity inhibition following ticagrelor loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome

Author: Thomas Cuisset, Vassili Panagides, Marc Laine, Caroline Gouarne, Franck Paganelli, Julien Mancini, Franck Thuny, Bernard Jouve, Marie-Christine Alessi, Corinne Frere, Laurent Bonello, Service de cardiologie [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier d'Aix en Provence [Aix-en-Provence] (CHIAP ), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Environnement Ville Société (EVS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Lyon (ENSAL)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Nationale des Travaux Publics de l'État (ENTPE)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], École normale supérieure - Lyon (ENS Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA), Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, platelet reactivity, ADP receptor blockers, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, VASP index, 0302 clinical medicine, Risk Factors, Clinical endpoint, Prospective Studies, Non-ST Elevated Myocardial Infarction, Microfilament Proteins, Hematology, Middle Aged, Clopidogrel, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], Treatment Outcome, Cardiology, Female, Stents, France, Ticagrelor, medicine.drug, Blood Platelets, Acute coronary syndrome, medicine.medical_specialty, Hemorrhage, Loading dose, ticagrelor, acute coronary syndrome, 03 medical and health sciences, Percutaneous Coronary Intervention, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, cardiovascular diseases, Aged, business.industry, Coronary Thrombosis, Percutaneous coronary intervention, medicine.disease, Phosphoproteins, Platelet Activation, Conventional PCI, ST Elevation Myocardial Infarction, business, Cell Adhesion Molecules, Mace, Biomarkers, Platelet Aggregation Inhibitors
Abstract: 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.
Published: 2019

36. Women, thrombosis, and cancer

Author: Ludovic Doucet, Corinne Frere, Dominique Farge, Christine Le Maignan, Service de Médecine Interne [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), McGill University = Université McGill [Montréal, Canada], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Internal medicine, Neoplasms, Antithrombotic, medicine, Humans, cardiovascular diseases, Stage (cooking), Hormone therapy, Cancer, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Anticoagulant, Thrombosis, Women's health issues, Hematology, medicine.disease, equipment and supplies, 3. Good health, [SDV] Life Sciences [q-bio], Contraception, 030220 oncology & carcinogenesis, Female, business, Complication, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Venous thromboembolism
Abstract: 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.
Published: 2019

37. Incidence of Venous Thromboembolism in Patients With Newly Diagnosed Pancreatic Cancer and Factors Associated With Outcomes

Author: Corinne Frere, Barbara Bournet, Sophie Gourgou, Julien Fraisse, Cindy Canivet, Jean M. Connors, Louis Buscail, Dominique Farge, Nicolas Carrère, Fabrice Muscari, Bertrand Suc, Rosine Guimbaud, Corinne Couteau, Marion Deslandres, Pascale Rivera, Anne-Pascale Laurenty, Nadim Fares, Karl Barange, Janick Selves, Anne Gomez-Brouchet, Bertrand Napoléon, Bertrand Pujol, Fabien Fumex, Jérôme Desrame, Christine Lefort, Vincent Lepilliez, Rodica Gincul, Pascal Artru, Léa Clavel, Anne-Isabelle Lemaistre, Laurent Palazzo, Jérôme Cros, Sarah Tubiana, Nicolas Flori, Pierre Senesse, Pierre-Emmanuel Colombo, Emmanuelle Samail-Scalzi, Fabienne Portales, Claire Honfo Ga, Carine Plassot, Frédéric Bibeau, Marc Ychou, Pierre Guibert, Christelle de la Fouchardière, Matthieu Sarabi, Patrice Peyrat, Séverine Tabone-Eglinger, Caroline Renard, Guillaume Piessen, Stéphanie Truant, Alain Saudemont, Guillaume Millet, Florence Renaud, Emmanuelle Leteurtre, Patrick Gele, Eric Assenat, Jean-Michel Fabre, François-Régis Souche, Marie Dupuy, Anne-Marie Gorce-Dupuy, Jeanne Ramos, Jean-François Seitz, Jean Hardwigsen, Emmanuelle Norguet-Monnereau, Philippe Grandval, Muriel Duluc, Dominique Figarella-Branger, Véronique Vendrely, Clément Subtil, Eric Terrebonne, Jean-Frédéric Blanc, Etienne Buscail, Jean-Philippe Merlio, Jean-Marc Gornet, Daniela Geromin, Geoffroy Vanbiervliet, Anne-Claire Frin, Delphine Ouvrier, Marie-Christine Saint-Paul, Philippe Berthelémy, Chelbabi Fouad, Stéphane Garcia, Nathalie Lesavre, Mohamed Gasmi, Marc Barthet, Vanessa Cottet, Cyrille Delpierre, CCSD, Accord Elsevier, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), McGill University Health Center [Montreal] (MUHC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), and CHU Toulouse [Toulouse]
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Time Factors, medicine.drug_class, Low molecular weight heparin, Pancreatic Cancer, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Clinical endpoint, medicine, Humans, Cumulative incidence, cardiovascular diseases, Progression-free survival, Prospective Studies, Aged, Neoplasm Staging, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, business.industry, Prognostic Factor, Incidence (epidemiology), Incidence, Hazard ratio, Gastroenterology, Venous Thromboembolism, Middle Aged, medicine.disease, Primary tumor, Confidence interval, Progression-Free Survival, 3. Good health, Pancreatic Neoplasms, 030104 developmental biology, 030211 gastroenterology & hepatology, Female, Blood Clot, France, business, Complication, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Carcinoma, Pancreatic Ductal, Follow-Up Studies
Abstract: 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).
Published: 2019

38. Automated differential white blood cell count and cytological analysis can detect near-tetraploid cells in chronic lymphoproliferative disorders

Author: Catherine Settegrana, Frederic Davi, Florence Nguyen-Khac, Adrien Cosson, Sylvain Choquet, Karim Maloum, Veronique Leblond, Elise Chapiro, Corinne Frere, CHU Pitié-Salpêtrière [APHP], Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service d'Hématologie clinique [CHU Pitié-Salpêtrière]
Subjects: Male, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Karyotype, Clinical Biochemistry, Lymphoproliferative disorders, Sensitivity and Specificity, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, Aged, 80 and over, Automation, Laboratory, 0303 health sciences, Laboratory methods, business.industry, Biochemistry (medical), Wbc differential, Reproducibility of Results, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoproliferative Disorders, 3. Good health, Tetraploidy, Leukemia, Chronic disease, 030220 oncology & carcinogenesis, Chronic Disease, Cytogenetic Analysis, Female, business
Abstract: International audience
Published: 2019

39. WITHDRAWN: Women, thrombosis, and cancer

Author: Dominique Farge, Ludovic Doucet, Christine Le Maignan, Corinne Frere, and Groupe francophone thrombose et cancer
Subjects: medicine.medical_specialty, Inclusion (disability rights), Feature (computer vision), business.industry, Family medicine, medicine, Cancer, Hematology, medicine.disease, business, Thrombosis
Abstract: This article has been withdrawn at the request of the publisher. The article was submitted for inclusion in the Supplement of full papers from the 8th International Symposium on Women's Health Issues in Thrombosis and Haemostasis (WHITH), to be published in 2019, but on acceptance it was mistakenly treated as if it were a regular article in the Journal. The article will feature in the Supplement. The Publisher apologizes to the authors of this article and to readers for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal .
Published: 2019

40. The best direct-acting oral anticoagulant for treatment of venous thromboembolism?

Author: Dominique Farge, Corinne Frere, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: medicine.medical_specialty, Pyridones, [SDV]Life Sciences [q-bio], MEDLINE, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Rivaroxaban, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, Anticoagulants, Retrospective cohort study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Venous Thromboembolism, Hematology, 3. Good health, Oral anticoagulant, Pyrazoles, business, Venous thromboembolism, Direct acting, medicine.drug
Abstract: International audience
Published: 2019

41. Antithrombotic efficacy of bivalirudin compared to unfractionated heparin during percutaneous coronary intervention for acute coronary syndrome

Author: Marc Laine, Françoise Dignat-George, Laurence Camoin-Jau, Noémie Resseguier, Régis Guieu, Gilles Lemesle, Corinne Frere, Laurent Bonello, Pierre-Emmanuel Morange, Franck Paganelli, Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Departement de cardiologie, Université de la Méditerranée - Aix-Marseille 2, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Service de cardiologie [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition (C2VN), Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vascular research center of Marseille ( VRCM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Nutrition, obésité et risque thrombotique ( NORT ), Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital Nord [CHU - APHM], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants ( SPMC ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Aix Marseille Université ( AMU ), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques ( DS-ACI / UMR MD2 ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Aix Marseille Université ( AMU ), Département d'Hématologie [APHM - Assistance Publique - Hôpitaux de Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Cardiologie [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Assistance Publique - Hôpitaux de Marseille ( APHM ), ALESSI, Marie-Christine, and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Antithrombotic, Medicine, Bivalirudin, ComputingMilieux_MISCELLANEOUS, stent thrombosis, Hematology, General Medicine, Hirudins, Middle Aged, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, thrombin, Recombinant Proteins, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, surgical procedures, operative, platelet aggregation, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cardiology, Female, Bolus (digestion), Ticagrelor, medicine.drug, Blood Platelets, Acute coronary syndrome, medicine.medical_specialty, Acute myocardial infarction, Loading dose, MESH: ACTIVATED CLOTTING TIME, ACUTE STENT THROMBOSIS, ANTICOAGULANTS, TICAGRELOR, INHIBITORS, PRASUGREL, PCI, 03 medical and health sciences, Percutaneous Coronary Intervention, Fibrinolytic Agents, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Humans, cardiovascular diseases, Acute Coronary Syndrome, Blood Coagulation, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Heparin, Percutaneous coronary intervention, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Thrombosis, medicine.disease, Peptide Fragments, 030104 developmental biology, Conventional PCI, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract: International audience; Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non– ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.
Published: 2019

42. Recent Advances in the Management of Cancer-Associated Thrombosis: New Hopes but New Challenges

Author: I. Benzidia, Dominique Farge, Zora Marjanovic, Corinne Frere, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), McGill University = Université McGill [Montréal, Canada], Gestionnaire, Hal Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Cancer Research, medicine.medical_specialty, Standard of care, medicine.drug_class, venous thromboembolism, Low molecular weight heparin, [SDV.CAN]Life Sciences [q-bio]/Cancer, direct oral anticoagulant, Review, 030204 cardiovascular system & hematology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Health care, medicine, Cancer associated thrombosis, cancer, In patient, cardiovascular diseases, Intensive care medicine, business.industry, low molecular weight heparin, Cancer, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, equipment and supplies, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Ambulatory, business, Venous thromboembolism
Abstract: International audience; Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients and leads to a significant increase in health care costs. Cancer patients often suffer from multiple co-morbidities and have both a greater risk of VTE recurrence and bleeding compared to non-cancer patients. Anticoagulation is therefore challenging. For many years, long-term therapy with Low-Molecular-Weight Heparin (LMWH) was the standard of care for the management of cancer-associated VTE. Direct oral anticoagulants (DOAC), which offer the convenience of an oral administration and have a rapid onset of action, have recently been proposed as a new option in this setting. Head-to-head comparisons between DOAC and LMWHs for the treatment of established VTE are now available, and data on the efficacy and safety of these drugs for primary prophylaxis of VTE in ambulatory cancer patients receiving systemic anticancer therapy are emerging. This narrative review aims to summarize the main recent advances in the prevention and treatment of cancer-associated VTE, including recent data on the use of individualized factors to stratify the risk of VTE in each individual patient, quality-of-life in patients treated with LMWH, and the place that DOACs will likely take in the cancer-associated VTE management landscape.
Published: 2018

43. OC-04 Incidence, predictors and clinical outcomes of venous thromboembolism in patients with newly diagnosed pancreatic ductal adenocarcinoma: results of the prospective BACAP-VTE study

Author: Corinne Frere, L. Buscail, Cindy Canivet, Barbara Bournet, S. Gourgou, J. Fraisse, Jean M. Connors, and Dominique Farge
Subjects: medicine.medical_specialty, Pancreatic ductal adenocarcinoma, business.industry, Internal medicine, Incidence (epidemiology), Medicine, In patient, Hematology, Newly diagnosed, business, Venous thromboembolism, Gastroenterology
Published: 2021

44. Antiphospholipid antibodies and thrombotic events in COVID-19 patients hospitalized in medicine ward

Author: Matheus Vieira, David Saadoun, Patrice Cacoub, Pascale Ghillani-Dalbin, Alexandre Le Joncour, Joe-Elie Salem, Isabelle Martin-Toutain, Olivier Benveniste, Georgina Maalouf, Anne-Geneviève Marcelin, Yves Allenbach, Paul Gougis, Corinne Frere, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Service d'Immunologie [CHU Pitié-Salpétrière], Service de virologie [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Immunology, MEDLINE, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Immunology and Allergy, Humans, Prospective Studies, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, 030203 arthritis & rheumatology, Aged, 80 and over, biology, business.industry, SARS-CoV-2, Antiphospholipid antibodies, Pulmonary embolism, COVID-19, Thrombosis, Middle Aged, medicine.disease, 3. Good health, Hospitalization, biology.protein, Antibodies, Antiphospholipid, Female, Antibody, business
Abstract: International audience
Published: 2020

45. Platelet Reactivity

Author: Laurent Bonello, Marc Laine, and Corinne Frere
Subjects: Aspirin, medicine.medical_specialty, business.industry, medicine.medical_treatment, Percutaneous coronary intervention, 030204 cardiovascular system & hematology, Clopidogrel, medicine.disease, Thrombosis, Surgery, Platelet reactivity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Cardiology, Platelet, 030212 general & internal medicine, Purinergic P2Y Receptor Antagonists, Cardiology and Cardiovascular Medicine, business, Prospective cohort study, medicine.drug
Published: 2017

46. Platelet reactivity inhibition following ticagrelor-loading dose in patients undergoing percutaneous coronary intervention for acute coronary syndrome

Author: Marc Laine, Caroline Gouarne, Franck Thuny, Laurent Bonello, Thomas Cuisset, Marie-Christine Alessi, Julien Mancini, Corinne Frere, Bernard Jouve, Franck Paganelli, and Vassili Panagides
Subjects: medicine.medical_specialty, Acute coronary syndrome, business.industry, medicine.medical_treatment, Percutaneous coronary intervention, medicine.disease, Clopidogrel, Loading dose, Internal medicine, Conventional PCI, medicine, Clinical endpoint, Cardiology, cardiovascular diseases, Cardiology and Cardiovascular Medicine, business, Ticagrelor, Mace, medicine.drug
Abstract: 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, data regarding PR from ticagrelor and the outcomes are lacking. Purpose We 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 (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 LD. The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR. Results Among the included 530 patients with ACS, 185 (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 Academic Research Consortium ≥ 2 events were recorded. Neither MACE nor bleeding were associated with PR (P = 0.34and 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. Conclusion In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP does not predict MACE or bleeding, but it is significantly associated with the occurrence of definite acute ST.
Published: 2020

47. Meta-Analysis of Potent P2Y12-ADP Receptor Antagonist Therapy Compared to Clopidogrel Therapy in Acute Coronary Syndrome Patients with Chronic Kidney Disease

Author: Etienne Puymirat, Laurent Bonello, Franck Thuny, Marc Laine, Thibaut Dabry, Dirk Sibbing, Julien Mancini, Stéphane Burtey, Daniel Aradi, Gilles Lemesle, Corinne Frere, Franck Paganelli, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [Hôpital Nord - APHM], Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Semmelweis University [Budapest], Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Ludwig-Maximilians-Universität München (LMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre recherche en CardioVasculaire et Nutrition (C2VN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Prémilleux, Annick, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Acute coronary syndrome, medicine.medical_specialty, Ticagrelor, Prasugrel, Drug-Related Side Effects and Adverse Reactions, [SDV]Life Sciences [q-bio], Administration, Oral, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Odds Ratio, Humans, 030212 general & internal medicine, Acute Coronary Syndrome, Renal Insufficiency, Chronic, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, business.industry, Hazard ratio, Hematology, medicine.disease, Clopidogrel, Survival Analysis, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Purinergic P2Y Receptor Antagonists, France, business, Prasugrel Hydrochloride, Mace, medicine.drug, Kidney disease
Abstract: Background The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk–benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown. Objective We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS. Methods We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings. Results We included data from three sub-group analysis of randomized clinical trials and two prospective observational studies (n = 31,234). Overall, PPAs were associated with lower rates of major cardiovascular events, with a pooled hazard ratio (pHR) of 0.88 (95% confidence interval [CI]: 0.79–0.99; p = 0.03), without increased bleedings (pHR = 1.10) (95% CI: 0.95–1.27; p = 0.18). In a sensitivity analysis restricted to studies enrolling invasively managed patients, the benefit of PPA on MACE was maintained (pHR = 0.85) (95% CI: 0.77–0.93; p Conclusion Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.
Published: 2018

48. 2019 international clinical practice guidelines for the treatment of venous thromboembolism – Authors' reply

Author: James D. Douketis, Dominique Farge, Cancer Initiative members, and Corinne Frere
Subjects: Clinical Practice, medicine.medical_specialty, Oncology, business.industry, Neoplasms, MEDLINE, Anticoagulants, Humans, Medicine, Venous Thromboembolism, business, Intensive care medicine, Venous thromboembolism
Published: 2019

49. Clinical Course of Venous Thromboembolism in Patients with Pancreatic Cancer: Insights from the RIETE Registry

Author: Javier Trujillo-Santos, Roberto Quintavalla, Corinne Frere, Ángel Sampériz, Manuel Monreal, Jorge Lima, José González-Martínez, Fernando J. Vazquez, Carme Font, and Dominique Farge
Subjects: Research design, Risk, medicine.medical_specialty, Letter to the editor, MEDLINE, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Text mining, Pharmacotherapy, Drug Therapy, Internal medicine, Pancreatic cancer, Thromboembolism, medicine, Humans, Registries, Neoplasm Metastasis, Survival analysis, business.industry, Incidence (epidemiology), Incidence, Anticoagulants, Hematology, medicine.disease, Survival Analysis, Pancreatic Neoplasms, Research Design, Spain, 030220 oncology & carcinogenesis, Neoplasm Recurrence, Local, business
Published: 2018

50. To Have and Have Not: Intrinsic Platelet Hyperreactivity?

Author: Marc Laine, Laurent Bonello, and Corinne Frere
Subjects: Male, ADP, collagen, platelet reactivity, Time Factors, Platelet aggregation, platelet function, Plaque growth, Coronary Artery Disease, 030204 cardiovascular system & hematology, antiplatelet, Coronary artery disease, risk prediction, 0302 clinical medicine, Risk Factors, P2RY12 receptor thrombosis, Coronary Heart Disease, Platelet, 030212 general & internal medicine, Longitudinal Studies, Original Research, Incidence, Middle Aged, Prognosis, stroke, Adenosine Diphosphate, Editorial, myocardial infarction, Massachusetts, Cardiovascular Diseases, platelet aggregation, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, medicine.drug, Blood Platelets, Platelets, medicine.medical_specialty, Acute coronary syndrome, Ticlopidine, Platelet Function Tests, Risk Assessment, acute coronary syndrome, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, cardiovascular diseases, epinephrine, Thrombus, business.industry, Editorials, Thrombosis, medicine.disease, Atherosclerosis, Cerebrovascular Disease/Stroke, business, Biomarkers, Progressive disease
Abstract: Background Platelet function is associated with adverse events in patients with cardiovascular disease (CVD). Methods and Results We examined associations of baseline platelet function with incident CVD events in the community‐based FHS (Framingham Heart Study). Participants free of prevalent CVD and without recent aspirin treatment with available data in the Framingham Offspring cohort (1991–1995) and Omni cohort (1994–1998) were included. Platelet function was measured with light transmission aggregometry using collagen (1.9 μg/mL), ADP (0.05–15 μmol/L), and epinephrine (0.01–15 μmol/L). We used proportional hazards models to analyze incident outcomes (myocardial infarction/stroke, CVD, and CVD mortality) with respect to platelet measures. The study sample included 2831 participants (average age, 54.3 years; 57% women). During follow‐up (median, 20.4 years), we observed 191 composite incident myocardial infarction or stroke events, 432 incident CVD cases, and 117 CVD deaths. Hyperreactivity to ADP and platelet aggregation at ADP concentration of 1.0 μmol/L were significantly associated with incident myocardial infarction/stroke in a multivariable model (hazard ratio, 1.68 [95% confidence interval, 1.13–2.50] [P=0.011] for hyperreactivity across ADP doses; and hazard ratio, 1.16 [95% confidence interval, 1.02–1.33] [P=0.029] for highest quartile of ADP response at 1.0 μmol/L versus others). No association was observed for collagen lag time or any epinephrine measures with incident myocardial infarction or stroke. Conclusions Intrinsic hyperreactivity to low‐dose ADP in our community‐based sample, who were free of CVD and any antiplatelet therapy, is associated with future arterial thrombosis during a 20‐year follow‐up. These findings reinforce ADP activation inhibition as a critical treatment paradigm and encourage further study of ADP inhibitor‐refractive populations.
Published: 2018

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