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1. APOLD1 loss causes endothelial dysfunction involving cell junctions, cytoskeletal architecture, and Weibel-Palade bodies, while disrupting hemostasis

Author

Simon Stritt, Paquita Nurden, Alan T. Nurden, Jean-François Schved, Jean-Claude Bordet, Maguelonne Roux, Marie-Christine Alessi, David-Alexandre Trégouët, Taija Mäkinen, and Muriel Giansily-Blaizot

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Vascular homeostasis is impaired in various diseases thereby contributing to the progression of their underlying pathologies. The endothelial immediate early gene Apolipoprotein L domain-containing 1 (APOLD1) helps to regulate endothelial function. However, its precise role in endothelial cell biology remains unclear. We have localized APOLD1 to endothelial cell contacts and to Weibel-Palade bodies (WPB) where it associates with von Willebrand factor (VWF) tubules. Silencing of APOLD1 in primary human endothelial cells disrupted the cell junction-cytoskeletal interface, thereby altering endothelial permeability accompanied by spontaneous release of WPB contents. This resulted in an increased presence of WPB cargoes, notably VWF and angiopoietin-2 in the extracellular medium. Autophagy flux, previously recognized as an essential mechanism for the regulated release of WPB, was impaired in the absence of APOLD1. In addition, we report APOLD1 as a candidate gene for a novel inherited bleeding disorder across three generations of a large family in which an atypical bleeding diathesis was associated with episodic impaired microcirculation. A dominant heterozygous nonsense APOLD1:p.R49* variant segregated to affected family members. Compromised vascular integrity resulting from an excess of plasma angiopoietin-2, and locally impaired availability of VWF may explain the unusual clinical profile of APOLD1:p.R49* patients. In summary, our findings identify APOLD1 as an important regulator of vascular homeostasis and raise the need to consider testing of endothelial cell function in patients with inherited bleeding disorders without apparent platelet or coagulation defects.

Published
2022
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2. Adaptation of recombinant activated factor VII in the treatment of acquired haemophilia A: Results from a prospective study (ACQUI-7) in France

Author

Benoît Guillet, Achille Aouba, Annie Borel-Derlon, Jeanne Yvonne Borg, Jean-François Schved, Hélène Schneid, and Hervé Lévesque

Subjects
Acquired haemophilia A, Bleeding episode, Bypassing agents, Daily-use rFVIIa, Observational, Prospective, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: The efficacy and safety of recombinant activated factor VII (rFVIIa; NovoSeven®) in patients with acquired haemophilia A (AHA) are established; however, data on daily use in clinical practice for bleeding episodes are limited. The ACQUI-7 study aimed to provide additional data on managing bleeding episodes with rFVIIa in patients with AHA. Methods: ACQUI-7, a prospective, observational, multicentre study in 20 sites in France, recruited patients from 2010 to 2013. Treatment was by physician’s judgement and therapeutic practice at each site. Inclusion criteria: anti-factor VIII (FVIII) auto-antibodies ​> ​1 Bethesda Unit, FVIII activity ​

Published
2021
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5. Iron overload in HFE C282Y heterozygotes at first genetic testing: a strategy for identifying rare HFE variants

Author

Patricia Aguilar-Martinez, Bernard Grandchamp, Séverine Cunat, Estelle Cadet, François Blanc, Marlène Nourrit, Kaiss Lassoued, Jean-François Schved, and Jacques Rochette

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background Heterozygotes for the p.Cys282Tyr (C282Y) mutation of the HFE gene do not usually express a hemochromatosis phenotype. Apart from the compound heterozygous state for C282Y and the widespread p.His63Asp (H63D) variant allele, other rare HFE mutations can be found in trans on chromosome 6.Design and Methods We performed molecular investigation of the genes implicated in hereditary hemochromatosis in six patients who presented with iron overload but were simple heterozygotes for the HFE C282Y mutation at first genetic testing. Functional impairment of new variants was deduced from computational methods including molecular modeling studies.Results We identified four rare HFE mutant alleles, three of which have not been previously described. One mutation is a 13-nucleotide deletion in exon 6 (c.1022_1034del13, p.His341_Ala345>LeufsX119), which is predicted to lead to an elongated and unstable protein. The second one is a substitution of the last nucleotide of exon 2 (c.340G>A, p.Glu114Lys) which modifies the relative solvent accessibility in a loop interface. The third mutation, p.Arg67Cys, also lies in exon 2 and introduces a destabilization of the secondary structure within a loop of the α1 domain. We also found the previously reported c.548T>C (p.Leu183Pro) missense mutation in exon 3. No other known iron genes were mutated. We present an algorithm at the clinical and genetic levels for identifying patients deserving further investigation.Conclusions Our results suggest that additional mutations in HFE may have a clinical impact in C282Y carriers. In conjunction with results from previously described cases we conclude that an elevated transferrin saturation level and elevated hepatic iron index should indicate the utility of searching for further HFE mutations in C282Y heterozygotes prior to other iron gene studies.

Published
2011
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6. The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance

Author

Patricia Aguilar-Martinez, Michael Bismuth, François Blanc, Pierre Blanc, Severine Cunat, Olivier Dereure, Pierre Dujols, Muriel Giansily-Blaizot, Christian Jorgensen, Amadou Konate, Dominique Larrey, Alain Le Quellec, Thibault Mura, Isabelle Raingeard, Jeanne Ramos, Eric Renard, Florence Rousseau, Jean-François Schved, and Marie-Christine Picot

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background Despite great progress in understanding the mechanisms underlying genetic hemochromatosis, data on the prevalence and the penetrance of the disorder are conflicting.Design and Methods A registry of patients with genetic hemochromatosis was established in the South of France and a regional health network was developed to allow the inclusion of all the diagnosed patients. C282Y homozygous patients classified in stages 2 (biological iron overload), 3 and 4 (clinical manifestations of iron overload, stage 4 being the more severe) according to the classification of the French National Authority for Health were included in the registry over a 6-year period.Results A total of 352 symptomatic C282Y homozygotes were identified, resulting in a total prevalence of 1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per 10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1% in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in subjects between 50 and 54 years old. Among 249 patients with complete records, 24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4. There was a higher proportion of males, and excessive alcohol intake was more prevalent in stage 4 than in stages 2 and 3 combined.Conclusions A French Mediterranean regional hemochromatosis registry with strict inclusion criteria is a useful tool for characterizing the history of this disease, particularly for the most severely affected patients, as defined by the disease severity classification. The total prevalence of symptomatic C282Y homozygotes in the region was found to be low. However, clinical penetrance (stages 3 and 4) was not negligible.

Published
2010
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7. Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab

Author

Dominique Helley, Régis Peffault de Latour, Raphaël Porcher, Celso Arrais Rodrigues, Isabelle Galy-Fauroux, Jeanne Matheron, Arnaud Duval, Jean-François Schved, Anne-Marie Fischer, and Gérard Socié

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background Paroxysmal nocturnal hemoglobinuria (PNH) is associated with an increased risk of thrombosis through unknown mechanisms.Design and Methods We studied 23 patients with PNH, before and after five and 11 weeks of treatment with eculizumab. We examined markers of thrombin generation and reactional fibrinolysis (prothrombin fragment 1+2 (F1+2), D-dimers, and plasmin antiplasmin complexes (P-AP), and endothelial dysfunction tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), soluble thrombomodulin (sTM), intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule (sVCAM-1), endothelial microparticles (EMPs), and tissue factor pathway inhibitor (TFPI).Results At baseline, vWF, sVCAM-1, the EMP count, and F1+2 and D-dimer levels were significantly elevated in the patients, including those with no history of clinical thrombosis. Treatment with eculizumab was associated with significant decreases in plasma markers of coagulation activation (F1+2, P=0.012, and D-dimers, P=0.01), and reactional fibrinolysis (P-AP, P=0.0002). Eculizumab treatment also significantly reduced plasma markers of endothelial cell activation (t-PA, P=0.0005, sVCAM-1, P

Published
2010
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8. Expression map of the human exome in CD34+ cells and blood cells: increased alternative splicing in cell motility and immune response genes.

Author

Sylvie Tondeur, Céline Pangault, Tanguy Le Carrour, Yoann Lannay, Rima Benmahdi, Aurélie Cubizolle, Said Assou, Véronique Pantesco, Bernard Klein, Samir Hamamah, Jean-François Schved, Thierry Fest, and John De Vos

Subjects
Medicine, Science
Abstract

BackgroundHematopoietic cells are endowed with very specific biological functions, including cell motility and immune response. These specific functions are dramatically altered during hematopoietic cell differentiation, whereby undifferentiated hematopoietic stem and progenitor cells (HSPC) residing in bone marrow differentiate into platelets, red blood cells and immune cells that exit into the blood stream and eventually move into lymphoid organs or inflamed tissues. The contribution of alternative splicing (AS) to these functions has long been minimized due to incomplete knowledge on AS events in hematopoietic cells.Principal findingsUsing Human Exon ST 1.0 microarrays, the entire exome expression profile of immature CD34+ HSPC and mature whole blood cells was mapped, compared to a collection of solid tissues and made freely available as an online exome expression atlas (Amazonia Exon! : http://amazonia.transcriptome.eu/exon.php). At a whole transcript level, HSPC strongly expressed EREG and the pluripotency marker DPPA4. Using a differential splicing index scheme (dsi), a list of 849 transcripts differentially expressed between hematopoietic cells and solid tissues was computed, that included NEDD9 and CD74. Some of these genes also underwent alternative splicing events during hematopoietic differentiation, such as INPP4B, PTPLA or COMMD6, with varied contribution of CD3+ T cells, CD19+ B cells, CD14+ or CD15+ myelomonocytic populations. Strikingly, these genes were significantly enriched for genes involved in cell motility, cell adhesion, response to wounding and immune processes.ConclusionThe relevance and the precision provided by this exon expression map highlights the contribution of alternative splicing to key feature of blood cells differentiation and function.

Published
2010
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10. Idiopathic purpura fulminans associated with anti-protein S antibodies in children: a multicenter case series and systematic review

Author

Amel Zerroukhi, Martha Duraes, Julien Baleine, Jean-François Schved, Isabelle Cau-Diaz, Tarik Kanouni, Elodie Boissier, Olivier Dautremay, Lionel Moulis, Alexandre Theron, Eric Jeziorski, Christine Biron-Andreani, and Michel Rodière

Subjects
medicine.medical_specialty, Delayed Diagnosis, medicine.medical_treatment, Werlhof's disease, Gastroenterology, Protein S, Chickenpox, Internal medicine, medicine, Humans, Multicenter Studies as Topic, Prospective Studies, Child, Coagulation Disorder, Retrospective Studies, biology, business.industry, Antithrombin, Hematology, respiratory system, medicine.disease, Stimulus Report, humanities, respiratory tract diseases, body regions, Platelet transfusion, Child, Preschool, Purpura Fulminans, biology.protein, Plasmapheresis, Fresh frozen plasma, business, medicine.drug
Abstract

Key Points IPF has a typical clinical presentation with involvement of the lower limbs corresponding to vascular territories.The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications in IPF., Visual Abstract, Idiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.

Published
2022

12. GFHT proposals for management of discordance between the International normalized ratio measured in the laboratory and by self-testing

Author

Dominique, Lasne, Ludovic, Drouet, Jean-François, Schved, Yves, Gruel, and Christine, Vinciguerra

Subjects
Societies, Scientific, Laboratory Proficiency Testing, medicine.medical_specialty, Vitamin K, Clinical Laboratory Techniques, business.industry, Anticoagulants, Reproducibility of Results, Thrombosis, Context (language use), 4-Hydroxycoumarins, General Medicine, Hematology, Reference Standards, Sensitivity and Specificity, Self-Testing, Indenes, Humans, Medicine, France, International Normalized Ratio, Reagent Kits, Diagnostic, Laboratories, business, Intensive care medicine
Abstract

The lack of quality control for patient point-of-care (POC) INR devices is an issue that has led the French health authorities to make recommendations: a laboratory INR (lab INR) has to be performed at the same time as the POC INR every 6 months. However, the differences observed between the two INRs, POC and lab INRs, are not necessarily due to a failure of the POC INR device. We present here a review of the different causes of discrepancies between INR results, which are the basis of the proposals of the Groupe français d'études sur l'hémostase et la thrombose (GFHT) on the management of lab and POC INR discrepancies. Pre-analytical conditions may account for discrepancies (sampling, transport and storage conditions), as well as analytical factors (mainly the nature of the thromboplastin used) and the clinical context (inflammatory or autoimmune diseases, polycythaemia...). The interpretation of INR discrepancies is not always easy and these proposals aim at standardizing the procedure to be followed in order to make the most appropriate decision for the patient.

Published
2021

13. Global Seroprevalence of Pre-existing Immunity Against AAV5 and Other AAV Serotypes in People with Hemophilia A

Author

Robert Klamroth, Gregory Hayes, Tatiana Andreeva, Keith Gregg, Takashi Suzuki, Ismail Haroon Mitha, Brandon Hardesty, Midori Shima, Toni Pollock, Patricia Slev, Johannes Oldenburg, Margareth C. Ozelo, Natalie Stieltjes, Sabine-Marie Castet, Johnny Mahlangu, Flora Peyvandi, Rashid Kazmi, Jean-François Schved, Andrew D. Leavitt, Michael Callaghan, Brigitte Pan-Petesch, Doris V. Quon, Jayson Andrews, Alex Trinh, Mingjin Li, and Wing Yen Wong

Subjects
seropositivity, Prevention, Genetic Vectors, Medical Biotechnology, Clinical Sciences, adeno-associated virus, Dependovirus, Antibodies, Viral, Hemophilia A, Serogroup, Antibodies, Neutralizing, gene therapy, Antibodies, Seroepidemiologic Studies, antibody, Genetics, Molecular Medicine, Humans, Viral, Prospective Studies, Molecular Biology, Neutralizing, Biotechnology
Abstract

Adeno-associated virus (AAV)-mediated gene therapy may provide durable protection from bleeding events and reduce treatment burden for people with hemophilia A (HA). However, pre-existing immunity against AAV may limit transduction efficiency and hence treatment success. Global data on the prevalence of AAV serotypes are limited. In this global, prospective, noninterventional study, we determined the prevalence of pre-existing immunity against AAV2, AAV5, AAV6, AAV8, and AAVrh10 among people ≥12 years of age with HA and residual FVIII levels ≤2 IU/dL. Antibodies against each serotype were detected using validated, electrochemiluminescent-based enzyme-linked immunosorbent assays. To evaluate changes in antibody titers over time, 20% of participants were retested at 3 and 6 months. In total, 546 participants with HA were enrolled at 19 sites in 9 countries. Mean (standard deviation) age at enrollment was 36.0 (14.87) years, including 12.5% younger than 18 years, and 20.0% 50 years of age and older. On day 1, global seroprevalence was 58.5% for AAV2, 34.8% for AAV5, 48.7% for AAV6, 45.6% for AAV8, and 46.0% for AAVrh10. Considerable geographic variability was observed in the prevalence of pre-existing antibodies against each serotype, but AAV5 consistently had the lowest seroprevalence across the countries studied. AAV5 seropositivity rates were 51.8% in South Africa (n = 56), 46.2% in Russia (n = 91), 40% in Italy (n = 20), 37.2% in France (n = 86), 26.8% in the United States (n = 71), 26.9% in Brazil (n = 26), 28.1% in Germany (n = 89), 29.8% in Japan (n = 84), and 5.9% in the United Kingdom (n = 17). For all serotypes, seropositivity tended to increase with age. Serostatus and antibody titer were generally stable over the 6-month sampling period. As clinical trials of AAV-mediated gene therapies progress, data on the natural prevalence of antibodies against various AAV serotypes may become increasingly important.

Published
2022

14. Cover Image

Author

Miguel Escobar, Giancarlo Castaman, Santiago Bonanad Boix, Michael Callaghan, Philippe Moerloose, Jonathan Ducore, Cédric Hermans, Janna Journeycake, Cindy Leissinger, James Luck, Johnny Mahlangu, Wolfgang Miesbach, Ismail Haroon Mitha, Claude Négrier, Doris Quon, Michael Recht, Jean François Schved, Amy D. Shapiro, Robert Sidonio, Alok Srivastava, Oleksandra Stasyshyn, Kateryna V. Vilchevska, Michael Wang, Guy Young, W. Allan Alexander, Ahmad Al‐Sabbagh, Daniel Bonzo, Christopher Macie, Thomas A. Wilkinson, and Craig Kessler

Subjects
Hematology, General Medicine, Genetics (clinical)
Published
2021

15. Characterizing hospital pathways for the care of acquired hemophilia in France using comprehensive national health data

Author

B. Guillet, Jeanne-Yvonne Borg, H. Levesque, Jean-François Schved, Achille Aouba, École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), 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 ), CHU Pontchaillou [Rennes], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Hôpital Lapeyronie [Montpellier] (CHU), Novo Nordisk A/S., Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 )

Subjects
medicine.medical_specialty, Pediatrics, Databases, Factual, Epidemiology, [SDV]Life Sciences [q-bio], Population, 030204 cardiovascular system & hematology, Hemophilia A, Antibodies, Chronic disease, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, medicine, Humans, Hemophilia, education, Aged, National health, education.field_of_study, Public health, business.industry, Incidence, Gastroenterology, Factor VII, Hospitals, 3. Good health, Hospitalization, Acquired hemophilia, Observational study, Rituximab, France, business, Bypassing agent, 030215 immunology, medicine.drug
Abstract

International audience; PURPOSE: Acquired hemophilia (AH) is a rare, serious bleeding disorder most often associated with older age and life-threatening complications. The patient care pathway for AH is complex because of the different types of bleeding, the presence of comorbidities, and the heterogeneity of medical specialists who care for these patients. METHODS: This observational study used the French national PMSI (Programme de médicalisation des systèmes d’information) database to characterize patients with AH in real-life practice and analyze their hospital pathway. In total, 180 patients with AH were identified over a 5-year study period (January 2010 to December 2014), based on three criteria: bypassing agent use, International Classification of Diseases, 10th revision code allocation, and aged over 65 years. Comparison of the incidence rate of AH versus registry data validated the PMSI as an epidemiological database. RESULTS: Rituximab was prescribed more often (60/180; 33.3%) than expected following guidelines and was associated in half of cases to early infections (32/60; 53.3%), surgery procedures were frequently performed during the year before AH onset (29/159; 18.2%), which may suggest a triggering effect, extended hospital stays (median: 20 days) and mortality remaining high (66/180; 36.7%) that occurred mainly during the first month after AH diagnosis. Median costs and number of injections were comparable between recombinant activated factor VII and plasma-derived activated prothrombin complex concentrate. CONCLUSION: These findings could inform future medico-economic approaches in this AH population (duration of stays, bypassing agents, rituximab use, comorbidities, hospitalizations with infections).

Published
2021

16. Outpatient central venous access device insertion in very young children with severe haemophilia

Author

Hedi Bensadok, Marie-Agnès Champiat, Maud Maniora, Eric Jeziorski, Christine Biron-Andreani, Alain Rochette, Alexandre Theron, Jean-François Schved, Robert Navarro, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )

Subjects
Catheterization, Central Venous, MESH: Coagulants, Pediatrics, medicine.medical_specialty, MEDLINE, 030204 cardiovascular system & hematology, Hemophilia A, Haemophilia, 03 medical and health sciences, 0302 clinical medicine, Text mining, MESH: Central Venous Catheters, Outpatients, medicine, Central Venous Catheters, Humans, ComputingMilieux_MISCELLANEOUS, MESH: Catheterization, Central Venous, MESH: Humans, Coagulants, business.industry, MESH: Child, Preschool, Infant, MESH: Blood Coagulation Factors, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, MESH: Hemophilia A, medicine.disease, MESH: Infant, Blood Coagulation Factors, MESH: Outpatients, 3. Good health, Venous access, Child, Preschool, business, 030215 immunology
Abstract

International audience

Published
2020

17. Gestion des agents antiplaquettaires en cas de procédure invasive non programmée ou d’hémorragie. Propositions du Groupe d’intérêt en hémostase périopératoire (GIHP) et du Groupe français d’études sur l’hémostase et la thrombose (GFHT) en collaboration avec la Société française d’anesthésie et de réanimation (SFAR)

Author

Normand Blais, François Mullier, Dan Longrois, Nathalie Nathan, Serge Motte, S. Laporte, Juan V. Llau, Yves Gruel, Stéphanie Roullet, J. Guay, J.-L. Bosson, Philippe Nguyen, P. van Der Linden, Dominique Lasne, Annick Steib, P.E. Morange, Anne Godier, Pierre Albaladejo, Sophie Susen, Brigitte Ickx, Jerrold H. Levy, G. Pernod, Emmanuel Marret, Samia Madi-Jebara, Guy Meyer, Yves Ozier, David Faraoni, Fanny Bonhomme, E. van Belle, Jean-François Schved, Mikael Mazighi, André Vincentelli, Patrick Mismetti, J.L. Mas, P.M. Roy, Emmanuel de Maistre, Jean-Philippe Collet, Sylvie Schlumberger, Y. Huet, Pierre Fontana, Charles Marc Samama, Delphine Garrigue, J.Y. Borg, Nadia Rosencher, S. Belisle, Jean-François Hardy, Thomas Lecompte, P. Sié, D. Garrigue Huet, P. Zufferey, A. Borel-Derlon, A. Cohen, S. Lessire, G. Le Gal, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'anesthésiologie, and UCL - (MGD) Laboratoire de biologie clinique

Subjects
03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Agent antiplaquettaireChirurgieHémorragieThromboseAnesthésie locorégionale, 030202 anesthesiology, 030204 cardiovascular system & hematology
Abstract

Le Groupe d’intérêt en hémostase périopératoire (GIHP) et le Groupe français d’études sur l’hémostase et la thrombose (GFHT), en collaboration avec la Société française d’anesthésie et de réanimation (SFAR) ont fait des propositions de gestion des agents antiplaquettaires (AAP) pour une procédure invasive programmée. Ces propositions ont été discutées et validées par vote ; toutes sauf une ont fait l’objet d’un accord fort. La gestion des AAP dépend de leur indication et de la procédure considérée. Le risque hémorragique lié à la procédure invasive peut être divisé en bas, intermédiaire ou élevé, selon la possibilité ou non de réaliser la procédure sous traitement (sous respectivement bithérapie antiplaquettaire, aspirine en monothérapie ou aucun AAP). Si une interruption des AAP est indiquée avant la procédure, une dernière prise d’aspirine, clopidogrel, ticagrélor et prasugrel 3, 5, 5 et 7 jours avant la procédure est proposée. Le risque thrombotique associé à l’interruption des AAP doit être évalué en fonction de l’indication des AAP. Il est plus élevé chez les patients traités par bithérapie pour un stent coronaire que chez ceux traités par monothérapie pour une prévention cardiovasculaire, un antécédent d’accident vasculaire cérébral ischémique ou une artériopathie oblitérante des membres inférieurs. Ces propositions concernent aussi le rôle potentiel des tests fonctionnels plaquettaires, la gestion des AAP pour l’anesthésie locorégionale, centrale et périphérique, et pour la chirurgie cardiaque coronaire.

Published
2019

18. Kinetics of the coagulation cascade including the contact activation system: sensitivity analysis and model reduction

Author

Rodrigo Méndez Rojano, Didier Lucor, Franck Nicoud, Muriel Giansily-Blaizot, Alexandre Ranc, Jean-François Schved, Simon Mendez, Laboratoire d'Informatique pour la Mécanique et les Sciences de l'Ingénieur (LIMSI), Université Paris Saclay (COmUE)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université - UFR d'Ingénierie (UFR 919), Sorbonne Université (SU)-Sorbonne Université (SU)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11), Institut Montpelliérain Alexander Grothendieck (IMAG), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Saclay-Sorbonne Université - UFR d'Ingénierie (UFR 919), Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Saclay (COmUE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Work (thermodynamics), Computer science, [SDV]Life Sciences [q-bio], Bayesian inference, 0206 medical engineering, Kinetics, Flow (psychology), 02 engineering and technology, Models, Biological, Contact activation, Humans, Computer Simulation, Coagulation cascade modeling, Sensitivity (control systems), Blood Coagulation, [PHYS]Physics [physics], [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Mechanics of the fluids [physics.class-ph], Model reduction, Mechanical Engineering, Thrombin, Bayes Theorem, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Chemical reactor, 020601 biomedical engineering, Modeling and Simulation, MESH: Blood coagulation/physiology, Computor simulation, Sensitivity analysis, Reduction (mathematics), Biological system, Biotechnology
Abstract

International audience; Thrombus formation is one of the main issues in the development of blood-contacting medical devices. This article focuses on the modeling of one aspect of thrombosis, the coagulation cascade, which is initiated by the contact activation at the device surface and forms thrombin. Models exist representing the coagulation cascade by a series of reactions, usually solved in quiescent plasma. However, large parameter uncertainty involved in the kinetic models can affect the predictive capabilities of this approach. In addition, the large number of reactions of the kinetic models prevents their use in the simulation of complex flow configurations encountered in medical devices. In the current work, both issues are addressed to improve the applicability and fidelity of kinetic models. A sensitivity analysis is performed by two different techniques to identify the most sensitive parameters of an existing detailed kinetic model of the coagulation cascade. The results are used to select the form of a novel reduced model of the coagulation cascade which relies on eight chemical reactors only. Then, once its parameters have been calibrated thanks to the Bayesian inference, this model shows good predictive capabilities for different initial conditions.

Published
2019

19. Dictionnaire du sang

Author

Jean-François Schved and Jean-François Schved

Abstract

Si la médecine définit le sang comme un tissu liquide aux multiples fonctions, s'il est indispensable à la vie, protège l'organisme et en nourrit les cellules, il alimente aussi, depuis toujours, l'imaginaire des hommes. Le langage use de la métaphore ou du symbole qu'il peut représenter. Les religions l'ont honni ou magnifié, parfois fait couler.Son image réelle ou fantasmée s'est glissée dans le quotidien de tout homme. Aussi le sang trouve-t-il sa place dans l'art, dans la littérature – qu'il s'agisse de romans, contes ou poésies. La peinture, l'opéra, les chansons ou le cinéma, tout autant que la gastronomie, lui ouvrent leur espace. Il fait monde.Ce dictionnaire du sang n'est pas un dictionnaire médical mais évoque, sous forme d'articles, les multiples facettes de cet étrange fluide, exposé aux maladies, reflet tout à la fois de l'unité du vivant et de sa diversité.

Published
2024

20. Adaptation of recombinant activated factor VII in the treatment of acquired haemophilia A: Results from a prospective study (ACQUI-7) in France

Author

Hervé Levesque, Jean-François Schved, Annie Borel-Derlon, Benoît Guillet, Jeanne Yvonne Borg, Achille Aouba, and Hélène Schneid

Subjects
medicine.medical_specialty, Bleeding episodes, education.field_of_study, lcsh:Diseases of the circulatory (Cardiovascular) system, business.industry, Population, Hematology, Bethesda unit, Daily-use rFVIIa, Prospective, lcsh:RC666-701, Internal medicine, Acquired haemophilia, Activated factor VII, medicine, Bleeding episode, Observational study, In patient, Bypassing agents, Cardiology and Cardiovascular Medicine, Prospective cohort study, education, business, Observational, Acquired haemophilia A
Abstract

Background: The efficacy and safety of recombinant activated factor VII (rFVIIa; NovoSeven®) in patients with acquired haemophilia A (AHA) are established; however, data on daily use in clinical practice for bleeding episodes are limited. The ACQUI-7 study aimed to provide additional data on managing bleeding episodes with rFVIIa in patients with AHA. Methods: ACQUI-7, a prospective, observational, multicentre study in 20 sites in France, recruited patients from 2010 to 2013. Treatment was by physician’s judgement and therapeutic practice at each site. Inclusion criteria: anti-factor VIII (FVIII) auto-antibodies ​> ​1 Bethesda Unit, FVIII activity ​

Published
2021

21. Thrombophilia assessment in presence of a venous thromboembolic disease and therapeutic consequences: Evaluation of practices in general medicine (Languedoc-Roussillon Region)

Author

Isabelle Quéré, Jean-François Schved, A. Charvier, J.-P. Laroche, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)

Subjects
Male, medicine.medical_specialty, General Practice, 030204 cardiovascular system & hematology, Thrombophilia, MESH: Prognosis, MESH: Venous Thromboembolism, 03 medical and health sciences, MESH: Referral and Consultation, 0302 clinical medicine, Venous thromboembolic disease, General Practitioners, Predictive Value of Tests, Risk Factors, MESH: Risk Factors, MESH: General Practice, Humans, Medicine, Practice Patterns, Physicians', Intensive care medicine, Referral and Consultation, ComputingMilieux_MISCELLANEOUS, MESH: Humans, MESH: Middle Aged, business.industry, MESH: Thrombophilia, Venous Thromboembolism, Middle Aged, Prognosis, medicine.disease, MESH: Male, MESH: Predictive Value of Tests, 3. Good health, MESH: General Practitioners, MESH: France, MESH: Practice Patterns, Physicians', Female, Clinical Competence, France, MESH: Clinical Competence, Cardiology and Cardiovascular Medicine, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract

International audience

Published
2020

22. Major surgery management in patients with haemophilia A and inhibitors on emicizumab prophylaxis without global coagulation monitoring

Author

Corinne Garcia-Gournay, Alexandre Theron, Christine Biron-Andreani, Jean François Schved, Isabelle Diaz-Cau, Christian Leonardi, Alexandre Ranc, Elena Santagostino, Robert Navarro, Marion Dischino, Romuald Guy, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Clinique Les Franciscaines (ELSAN), Clinique Le Castelet, and Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Subjects
medicine.medical_specialty, Haemophilia A, MEDLINE, haemophilia A, 030204 cardiovascular system & hematology, 03 medical and health sciences, MESH: Antibodies, Bispecific, 0302 clinical medicine, inhibitors, medicine, Coagulation (water treatment), In patient, Emicizumab, emicizumab, MESH: Humans, MESH: Middle Aged, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, MESH: Hemophilia A, medicine.disease, major surgery, MESH: Male, 3. Good health, Surgery, MESH: Antibodies, Monoclonal, Humanized, business, 030215 immunology
Abstract

International audience; Patients with haemophilia and high-titre inhibitors were often denied surgery due to the high risk of perioperative bleeding. However, data on bypassing agents for the management of major orthopaedic surgery showed efficacy values between 81% and 85% for activated recombinant human factor VII (rFVIIa) (Novoseven®, Novo Nordisk, Bagsværd, Denmark) and between 81% and 91% for plasma-derived activated prothrombin complex concentrates (aPCC) (Giangrande et al., 2018).

Published
2020

23. Diagnosis and management of heparin-induced thrombocytopenia

Author

Yves Ozier, F. Mullier, P. Albaladejo, Grégoire Le Gal, Jean-François Schved, Sophie Susen, Jean-Philippe Collet, Emmanuel Marret, Yves Gruel, Jean-François Hardy, Claire Pouplard, N. Blais, D. Lasne, Sylvie Schlumberger, Thomas Lecompte, A. Vincentelli, J.Y. Borg, Brigitte Ickx, A. Godier, Guy Meyer, E de Maistre, Dan Longrois, Samia Madi-Jebara, Sophie Testa, Nathalie Nathan, Mikael Mazighi, André Vincentelli, Joanne Guay, S. Laporte, P.M. Roy, Emmanuel de Maistre, D. Garrigue Huet, P. Zufferey, Y. Huet, Nadia Rosencher, P. Van der Linden, Dominique Lasne, S. Roullet, Y. Gruel, François Mullier, P. Sié, Philippe Nguyen, David Faraoni, Normand Blais, Jerrold H. Levy, Annick Steib, P.E. Morange, S. Lessire, G. Le Gal, Juan V. Llau, Anne Godier, Sylvain Bélisle, Pierre Albaladejo, Serge Motte, Stéphanie Roullet, J.-L. Bosson, Patrick Mismetti, Fanny Bonhomme, Charles-Marc Samama, E. van Belle, J.L. Mas, Pierre Fontana, G. Pernod, S. Susen, A. Borel-Derlon, A. Cohen, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'anesthésiologie, UCL - (MGD) Laboratoire de biologie clinique, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Clinique, business.industry, MEDLINE, General Medicine, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, Gastroenterology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030220 oncology & carcinogenesis, Heparin-induced thrombocytopenia, Internal medicine, medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Heparin-induced thrombocytopenia (HIT) is a rare, iatrogenic disease characterised by its potential severity, mainly related to thrombosis, and by difficulties regarding its diagnosis and management of affected patients. In 2002, a conference of experts mobilised by the French Society of Anaesthesia and Intensive Care Medicine (Société française d’anesthésie et de réanimation [SFAR]) drafted recommendations for the management of HIT [...]

Published
2020

24. Inherited or acquired modifiers of iron status may dramatically affect the phenotype in dehydrated hereditary stomatocytosis

Author

Richard van Wijk, Corentin Orvain, Serge Pissard, Guillaume Cartron, Patricia Aguilar-Martinez, Lamisse Mansour-Hendili, Muriel Giansily-Blaizot, Lydie Da Costa, Séverine Cunat, Véronique Picard, and Jean-François Schved

Subjects
medicine.medical_specialty, business.industry, Hematology, General Medicine, Phlebotomy, medicine.disease, Phenotype, Hemolysis, 03 medical and health sciences, Red blood cell, 0302 clinical medicine, medicine.anatomical_structure, Endocrinology, 030220 oncology & carcinogenesis, Internal medicine, Transfusion requirement, Dehydrated hereditary stomatocytosis, medicine, Iron status, HAMP, business, 030215 immunology
Abstract

Severe iron overload is frequent in dehydrated hereditary stomatocytosis (DHSt) despite well-compensated hemolysis and no or little transfusion requirement. We investigated 4 patients with proven DHSt, in whom the degree of hemolysis was closely related to iron status. Genetic modifiers increasing iron stores (HFE:pCys282Tyr, HAMP:c-153C>T mutations) were accompanied with high liver iron concentrations and increased hemolysis, whereas therapeutic phlebotomies alleviated the hemolytic phenotype. There were no manifestations of hemolysis in one patient with low iron stores. Hemolysis reappeared when iron supplementation was given. The search for genetic or acquired modifiers of iron status and the modulation of iron stores may help in the management of these patients.

Published
2018

25. Anticoagulants oraux directs (AOD) : une mise au point nécessaire

Author

Jean-François Schved, F. Becker, and Jean-Pierre Laroche

Subjects
medicine.medical_specialty, Antivitamine k, business.industry, 030204 cardiovascular system & hematology, stomatognathic diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, Thrombotic disease, 030212 general & internal medicine, Medical prescription, Cardiology and Cardiovascular Medicine, Intensive care medicine, business
Abstract

In 2008, we decided to enter the era of direct oral anticoagulants (DOACS). Was that the right decision to make? The answer will depend on how well we meet the conditions of proper use. This means avoiding underdosing and overdosing as well as understanding how DOACS were validated so that our prescriptions fulfill their role in the management of thrombotic disease.

Published
2018

26. Utilité du TTR (temps passé dans la cible thérapeutique) dans le suivi des patients sous antivitamine K : analyse d’une cohorte de patients

Author

Isabelle Quéré, J.-P. Laroche, Jean-François Schved, Bertrand R. Caré, and E. Valdelièvre

Subjects
03 medical and health sciences, 0302 clinical medicine, 030212 general & internal medicine, 030204 cardiovascular system & hematology, Cardiology and Cardiovascular Medicine
Abstract

Resume Introduction Malgre l’essor des prescriptions d’anticoagulants oraux directs (AOD), les antagonistes de la vitamine K (antivitamines K [AVK]) restent le traitement de choix pour traiter et prevenir les evenements thromboemboliques au long cours. La morbi-mortalite des AVK est en partie due a la difficulte de maintenir le patient dans sa fourchette therapeutique. Pour les patients sous antivitamine K (AVK), le temps passe dans la zone therapeutique (time in therapeutic range [TTR]) est un parametre de qualite du traitement, largement utilise dans les essais cliniques mais rarement par les prescripteurs. Sa correlation avec le risque de survenue d’accident hemorragique ou thrombotique et la mortalite a ete etablie. Nous avons etudie ce parametre sur une cohorte de patients pour evaluer la qualite de leur suivi therapeutique et tenter d’identifier les facteurs de risque de mauvais TTR. Materiel et methode Nous avons inclus 3387 patients, soit 24 029 INR grâce a la collaboration de LaboSud Oc Biologie durant 4 mois. Nous avons calcule les TTR patient. Le laboratoire nous a transmis le sexe et l’âge de chacun des patients ainsi que la molecule AVK utilisee, la fourchette therapeutique et la specialite du medecin prescripteur. Nous avons alors analyse les odds ratio associes a ces facteurs. Resultats Le TTR moyen etait de 68 %, proche des TTR recommandes par les societes savantes. Le sexe feminin est le seul facteur statistiquement correle a un mauvais equilibre sous AVK (OR = 1,22, IC95 % : 1,06–1,39, p = 0,00552). De nombreux facteurs habituellement correles a un mauvais equilibre sous AVK n’ont pas ete etudies du fait d’un manque d’informations. Conclusion Avec, dans notre cohorte un TTR proche des 70 % recommandes, il n’y aurait pas de benefice en termes de securite a preferer les AOD pour les patients de l’Herault, surtout dans un contexte de restriction economique. Le suivi regulier du TTR individuel des patients et des TTR de cohorte devrait permettre d’optimiser la prise en charge des patients sous AVK.

Published
2018

27. Compliance with Early Long-Term Prophylaxis Guidelines for Severe Hemophilia A

Author

Paul Saultier, Yves Guillaume, Virginie Demiguel, Claire Berger, Annie Borel-Derlon, Ségolène Claeyssens, Annie Harroche, Caroline Oudot, Anne Rafowicz, Marc Trossaert, Bénédicte Wibaut, Christine Vinciguerra, Mohamed Boucekine, Karine Baumstarck, Sandrine Meunier, Thierry Calvez, Hervé Chambost, Achille Aouba, Faezeh Legrand, Chantal Rothschild, Marie-Françoise Torchet, Roseline d’Oiron, Thierry Lambert, Yves Laurian, Jennifer Biernat, Jenny Goudemand, Armelle Parquet, Véronique Tintillier, Anne Durin Assollant, Claude Négrier, Sabine Castet, Viviane Guérin, Yohann Huguenin, Marguerite Micheau, Anne Ryman, Hérve Chambost, Céline Falaise, Marie Françoise Thiercelin-Legrand, Marianne Fiks-Sigaud, Marc Fouassier, Edith Fressinaud, Sophie Voisin, Albert Faradji, Patrick Lutz, Marie Elisabeth Briquel, Birgit Frotscher, Béatrice Fimbel, Yves Gruel, Claude Guerois, Sandra Regina, Jean Baptiste Valentin, Christine Biron Andreani, Philippe Codine, Daniel Donadio, Robert Navarro, Paola Rospide, Jean-François Schved, Bénédicte Collet, Annie Borel Derlon, Philippe Gautier, Sophie Bayart, Ben⊚ıt Guillet, JeanneYvonne Borg, Cécile Dumesnil, Charline Normand, Pascale Schneider, Philippe Tron, Jean-Pierre Vannier, Fabienne Dutrillaux, Fabienne Volot, Piotr Gembara, Alain Marques-Verdier, Dalila Adjaoud, Claire Barro, Gilles Pernod, Ben⊚ıt Polack, Patricia Pouzol, Nadra Ounnoughene, Patricia Paugy, Valérie Robert, Natalie Stieltjes, Brigitte Bastenaire, Emmanuelle de Raucourt, Jocelyne Peynet, Valérie Li-Thiao-Te, Brigitte Pautard, Catherine Behar, Stéphanie Gorde, Martine Munzer, Valérie Gay, Elisabeth Benz Lemoine, Laurent Macchi, Lionel De Lumley, Solange Gaillard, Anne Deville, Fabrice Monpoux, Marie Anne Bertrand, Brigitte Pan-Petesch, Abel Hassoun, Brigitte Coatmelec, Philippe Beurrier, Michèle Damay, Philippe Moreau, Odile Pouille-Lievin, Caroline Schoepfer, Eliane Tarral, Monique Bianchin, Joël Nguyen, Olivier Pincemaille, Marie-Odile Peter, 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), Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpitaux de Saint Maurice (HNSM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Universitaire des Maladies Rénales [CHU Caen] (CUMR Caen), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Limoges, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Université de Montpellier (UM)

Subjects
Male, Pediatrics, medicine.medical_specialty, Multivariate analysis, [SDV]Life Sciences [q-bio], Population, Long term prophylaxis, Kaplan-Meier Estimate, Hemophilia A, Severe hemophilia A, Severity of Illness Index, Early initiation, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Humans, Medicine, Cumulative incidence, 030212 general & internal medicine, Practice Patterns, Physicians', education, Birth Year, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, education.field_of_study, business.industry, Infant, Newborn, Infant, Blood Coagulation Factors, Logistic Models, Child, Preschool, Practice Guidelines as Topic, Pediatrics, Perinatology and Child Health, Cohort, France, Guideline Adherence, Joint Diseases, business
Abstract

International audience; Objectives: To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline compliance.Study design: This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).Results: We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with "timely long-term prophylaxis" as compared with "delayed long-term prophylaxis": hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with "long-term prophylaxis guideline compliance" vs "long-term prophylaxis anticipation."Conclusions: This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.

Published
2021

28. Investigator clinical trials: How can we ask the question?

Author

Jean-François Schved

Subjects
Clinical Trials as Topic, medicine.medical_specialty, business.industry, Hematology, General Medicine, 030204 cardiovascular system & hematology, Research Personnel, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Drug development, Research Design, Ask price, medicine, Humans, Medical physics, business, Genetics (clinical), 030215 immunology
Abstract

The development of knowledge about a treatment requires clinical trials. In addition to the trials initiated by the industry, some trials called Investigator initiated trials (it is) are developed on the initiative of the investigator. The assay must provide answers to one or several questions concerning the drug studied, so it is essential to determine the exact form of the question. Through three examples of drug development in the field of haemorrhagic diseases, we try to identify the difficulties encountered in developing these trials and the risks of misinterpretation of the results of these trials.

Published
2020

29. Gestion des anticoagulants oraux directs pour la chirurgie et les actes invasifs programmés : propositions réactualisées du Groupe d’intérêt en hémostase périopératoire (GIHP) – septembre 2015

Author

Normand Blais, Patrick Mismetti, Emmanuel Marret, Pierre Fontana, Fanny Bonhomme, Sophie Susen, Annick Steib, Nadia Rosencher, Charles Marc Samama, Pierre Sié, Stéphanie Roullet, Dan Longrois, David Faraoni, Jean-François Schved, Jean-Philippe Collet, Juan V. Llau, Anne Godier, and Pierre Albaladejo

Subjects
03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, 030204 cardiovascular system & hematology
Abstract

Resume Depuis 2011, l’experience et les donnees concernant les patients traites par anticoagulants oraux directs (AOD) et beneficiant d’un acte invasif programme se sont enrichies. Dans le meme temps, un accroissement du risque hemorragique lors de la realisation de relais anticoagulants preoperatoires a ete mis en evidence, sans reduction du risque thrombotique. Ces donnees nouvelles conduisent a adapter les propositions emises par le GIHP en 2011. Pour les actes programmes a risque hemorragique faible, il est propose de ne pas prendre d’AOD la veille au soir ni le matin de l’intervention, quel que soit le schema therapeutique du patient ; et de reprendre le traitement selon le schema habituel du patient et au moins 6 heures apres la fin du geste invasif. Pour les actes invasifs a risque hemorragique eleve, il est propose une derniere prise a j–3 pour le rivaroxaban, l’apixaban et l’edoxaban ; une derniere prise de dabigatran a j–4 si la clairance de la creatinine est superieure a 50 mL/min, a j–5 si la clairance est comprise entre 30 et 50 mL/min. Dans le cas de la neurochirurgie intracrânienne et de l’anesthesie neuraxiale, des delais plus longs sont conseilles. Il n’y a plus de place pour les relais anticoagulants ni pour la mesure des concentrations d’AOD sauf situations exceptionnelles.

Published
2016

30. After the SIPPET study: Position paper of the CoMETH, the French society of haemophilia

Author

Sabine-Marie Castet, Bénédicte Wibaut, Aurélien Lebreton, Jean-François Schved, Céline Falaise, and Lucia Rugeri

Subjects
Pediatrics, medicine.medical_specialty, Factor VIII, business.industry, Treatment outcome, Study Position, Hematology, General Medicine, 030204 cardiovascular system & hematology, Hemophilia A, Haemophilia, medicine.disease, Recombinant Proteins, Isoantibodies, 03 medical and health sciences, Treatment Outcome, 0302 clinical medicine, medicine, Humans, France, business, Genetics (clinical), Randomized Controlled Trials as Topic, 030215 immunology
Published
2018

31. Design of a prospective observational study on the effectiveness and real-world usage of recombinant factor VIII Fc (rFVIIIFc) compared with conventional products in haemophilia A: The A-SURE study

Author

Johan Szamosi, Flora Peyvandi, Charles R. M. Hay, Jean François Schved, Bent Winding, Johannes Oldenburg, Stefan Lethagen, Víctor Jiménez-Yuste, UAM. Departamento de Medicina, and Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)

Subjects
Male, medicine.medical_specialty, Adolescent, Clinical effectiveness, Medicina, Recombinant Fusion Proteins, Haemophilia A, Hemorrhage, 030204 cardiovascular system & hematology, Hemophilia A, Non-interventional study, Recombinant factor viii, Perioperative Care, 03 medical and health sciences, 0302 clinical medicine, Recombinant factor VIII Fc, Informed consent, medicine, Protocol, Humans, Prospective Studies, Child, Propensity Score, Factor VIII, Dose-Response Relationship, Drug, business.industry, Confounding, Ethics committee, General Medicine, medicine.disease, Treatment Outcome, Emergency medicine, Propensity score matching, Observational study, business, 030215 immunology, Haematology (Incl Blood Transfusion), Half-Life
Abstract

Introduction: Haemophilia A is a rare bleeding disorder caused by coagulation factor VIII (FVIII) deficiency. This is treated with factor VIII, conventionally using products with a half-life of 8-12 hours typically administered every 2-3 days. Recombinant FVIII Fc (rFVIIIFc) represents a new generation of products with an extended half-life allowing higher FVIII levels and longer dosing interval. The efficacy and safety of rFVIIIFc have been established in clinical studies and several years of postmarketing use. However, there remains a need to compare treatment outcome with conventional products in routine clinical use. Methods and analysis: A-SURE is an ongoing, non-interventional European study with the primary objective to compare the clinical effectiveness of rFVIIIFc with conventional factor products used for haemophilia A prophylaxis. Data covering a 24-month prospective period and a 12-month retrospective period will be collected. Three primary endpoints: bleeding rate, injection frequency and factor consumption will be used to evaluate treatment outcomes. Enrolment of 175 patients on rFVIIIFc and 175 on conventional products is planned. All eligible patients from participating centres will be invited to participate. Visits and treatments follow routine clinical practice. Bias will be reduced by patient matching for age at baseline and the last weekly prophylaxis dose of a conventional product prior to baseline. Propensity scores will be calculated based on prognostic factors and potential confounders assessed at baseline and adjusted for in the estimation of the treatment effect. Ethics and dissemination: Study approval was obtained by local independent ethics committees and/or authorities, and informed consent from patients or their legal representative is a requirement for participation. Names of ethical committees and approval numbers are provided as supplementary information. The study results will be submitted for publication in a peer-reviewed scientific journal and presented at scientific conferences., This work was fully funded by Swedish Orphan Biovitrum AB (publ)

Published
2019

32. Eptacog beta: a novel recombinant human factor VIIa for the treatment of hemophilia A and B with inhibitors

Author

Christine Biron-Andreani and Jean-François Schved

Subjects
Glycosylation, Factor VIIa, Pharmacology, Hemophilia A, Hemophilia B, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, law, Medicine, Animals, Humans, Platelet, Beta (finance), Factor IX, Factor VII, business.industry, Hematology, Recombinant Proteins, chemistry, 030220 oncology & carcinogenesis, Pharmacodynamics, Recombinant DNA, Rabbits, business, 030215 immunology, medicine.drug
Abstract

INTRODUCTION Hemophilia A and B are X-linked recessive disorders caused by the deficiency of factor VIII or factor IX, respectively. Bleeding episodes are treated with factor replacement therapy. The most serious complication of this treatment is the development of inhibitors. In such patients, bypassing agents, such as activated recombinant human factor VII (rhFVIIa) or plasma-derived activated prothrombin complex concentrates, are administered to prevent or treat bleeding episodes. The high cost of the current bypassing agents limits their availability in emerging countries. Areas covered: Authors reviewed the published data on the development and clinical testing of eptacog beta, a new second-generation rhFVIIa produced in the milk of transgenic rabbits. The available data indicate that activated eptacog beta exhibits structural (N- and O- glycosylation), pharmacodynamic and pharmacokinetic characteristics similar to activated eptacog alfa, its main competitor, but binds slightly better to platelets and HUVEC, and it is safe and effective. Expert commentary: This critical review of available data on activated eptacog beta shows that it represents an alternative source of rhFVIIa at potentially lower cost with easily expandable manufacturing capacity that could contribute to cover the future patient needs.

Published
2018

33. Et je ne te laisserai pas seule

Author

Jean-François Schved and Jean-François Schved

Subjects
Suicide--Fiction, Children of depressed persons--Fiction
Abstract

Charlotte, dix-sept ans, a disparu du domicile de ses parents. Après trois mois de recherches et d'hypothèses, on retrouve son corps au pied d'une falaise. L'enquête immédiate conclut au suicide d'une jeune fille dépressive. Qu'est-ce qui a pu la pousser au geste final?

Published
2020

34. Management of invasive procedures in patients with platelet disorders or thrombocytopenia Guidelines by French expert group on inherited platelet diseases

Author

Jean-François Schved, Pierre Sié, and Yves Gruel

Subjects
medicine.medical_specialty, biology, business.industry, Platelet disorder, 030208 emergency & critical care medicine, Hematology, Expert group, Surgery, 03 medical and health sciences, 0302 clinical medicine, Von Willebrand factor, 030202 anesthesiology, Recombinant factor VIIa, biology.protein, Medicine, Platelet, In patient, business, Intensive care medicine, Desmopressin, Tranexamic acid, medicine.drug
Abstract

Les pathologies plaquettaires constitutionnelles (thrombopenies, thrombopathies ou association des deux) forment un ensemble tres heterogene de maladies rares dont le risque hemorragique spontane est variable, mais qui sont souvent revelees par un saignement excessif a l’occasion d’actes invasifs. Du fait de leur rarete, ces situations n’ont que rarement fait l’objet d’essais cliniques permettant des recommandations de haut niveau d’evidence. Le Centre de reference des thrombopathies constitutionnelles (CRTC) a etabli, sur la base d’une revue de la litterature et de l’experience de ses membres, un ensemble de recommandations concernant la prise en charge de ces patients, suivant les criteres de risque lies a l’acte invasif, a la pathologie en cause et a leurs antecedents et comorbidites. La place respective et les modalites d’utilisation des concentres plaquettaires et des traitements medicamenteux (antifibrinolytiques, desmopressine, facteur VIIa recombinant, facteur Willebrand, agonistes du recepteur de la thrombopoietine) sont presentees et discutees.

Published
2016

35. Influence of surgical bleeding on the relationship between admission coagulopathy and risk of massive transfusion: lesson from 704 severe trauma patients

Author

Pauline Deras, A. Dehon, Pascal Latry, Jean-François Schved, E. Boissier, Jonathan Charbit, Karim Lakhal, Xavier Capdevila, Hôpital Lapeyronie [Montpellier] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Adult, Male, Risk, medicine.medical_specialty, Adolescent, education, Acute trauma coagulopathy, Blood Loss, Surgical, 030204 cardiovascular system & hematology, Logistic regression, standard coagulation tests, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Odds Ratio, Coagulopathy, Humans, Medicine, Blood Transfusion, Retrospective Studies, Prothrombin time, Receiver operating characteristic, medicine.diagnostic_test, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, 030208 emergency & critical care medicine, Retrospective cohort study, prediction, Hematology, General Medicine, Blood Coagulation Disorders, Middle Aged, medicine.disease, prothrombin time, Surgery, ROC Curve, Severe trauma, Area Under Curve, trauma management, haemorrhagic shock, Wounds and Injuries, Population study, Female, Partial Thromboplastin Time, business, Packed red blood cells
Abstract

Background This study hypothesized that the relationship between early coagulopathy and massive transfusion (MT) in trauma was highly dependent on the presence of surgical bleeding. Methods Consecutive severe trauma patients admitted to our institution over a 4-year period were included in this retrospective study. Surgical bleeding was defined as an injury requiring an invasive endovascular or surgical haemostatic procedure. The ability of prothrombin time ratio (PTr) and activated partial thromboplastin time ratio (aPTTr) to predict MT (≥10 units of packed red blood cells during the first 24 h) was determined by ROC curves. The strength of association and interaction between PTr, surgical bleeding and MT was assessed using a logistic regression analysis. Results Among the 704 patients included (ISS 21·0 ± 16·2), MT rate was higher in patients with surgical bleeding than in those with no surgical bleeding (47% vs. 5%; P

Published
2016

36. Iatrogenic acquired factor V inhibitors: A case report and review of the French pharmacovigilance database

Author

Jean-Luc Faillie, Pauline Sauguet, Fabienne Vacheret, Sara Burcheri, Dominique Hillaire-Buys, Christine Biron-Andreani, Jean-François Schved, Alexandre Theron, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)

Subjects
medicine.medical_specialty, biology, Iatrogenic bleeding disorders, business.industry, Factor V, MEDLINE, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, 030204 cardiovascular system & hematology, Acquired factor V inhibitor, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Antibiotics, Pharmacovigilance, medicine, biology.protein, Iatrogenic disease, Intensive care medicine, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract

International audience

Published
2017

37. Anti‐A2 and anti‐A1 domain antibodies are potential predictors of immune tolerance induction outcome in children with hemophilia A

Author

Daniel Laune, Eve Mathieu-Dupas, J. Balicchi, Claude Granier, Jean-François Schved, Géraldine Lavigne-Lissalde, Priscilla Lapalud, Yves Gruel, Franck Molina, C. Rothschild, Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, immune tolerance, medicine.medical_specialty, Hemophilia A, Immune tolerance, Epitopes, Predictive Value of Tests, Internal medicine, medicine, Humans, Statistical analysis, fluoroimmunoassay, Child, Autoantibodies, Retrospective Studies, factor VIII, Factor VIII, Predictive marker, Receiver operating characteristic, Plasma samples, biology, Coagulants, business.industry, blood coagulation factor inhibitors, Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Predictive value, Protein Structure, Tertiary, 3. Good health, Treatment Outcome, ROC Curve, Area Under Curve, Child, Preschool, Immunoglobulin G, Immunology, biology.protein, hemophilia A, France, Immunotherapy, Antibody, Complication, business, Biomarkers
Abstract

International audience; BACKGROUND:Hemophilia A (HA) is a congenital bleeding disorder resulting from factor VIII deficiency. The most serious complication of HA management is the appearance of inhibitory antibodies (Abs) against injected FVIII concentrates. To eradicate inhibitors, immune tolerance induction (ITI) is usually attempted, but it fails in up to 30% of cases. Currently, no undisputed predictive marker of ITI outcome is available to facilitate the clinical decision.OBJECTIVES:To identify predictive markers of ITI efficacy.METHODS:The isotypic and epitopic repertoires of inhibitory Abs were analyzed in plasma samples collected before ITI initiation from 15 children with severe HA and high-titer inhibitors, and their levels were compared in the two outcome groups (ITI success [n = 7] and ITI failure [n = 8]). The predictive value of these candidate biomarkers and of the currently used indicators (inhibitor titer and age at ITI initiation, highest inhibitor titer before ITI, and interval between inhibitor diagnosis and ITI initiation) was then compared by statistical analysis (Wilcoxon test and receiver receiver operating characteristic [ROC] curve analysis).RESULTS:Whereas current indicators seemed to fail in discriminating patients in the two outcome groups (ITI success or failure), anti-A1 and anti-A2 Ab levels before ITI initiation appeared to be good potential predictive markers of ITI outcome (P < 0.018). ROC analysis showed that anti-A1 and anti-A2 Abs were the best at discriminating between outcome groups (area under the ROC curve of > 0.875).CONCLUSION:Anti-A1 and anti-A2 Abs could represent new promising tools for the development of ITI outcome prediction tests for children with severe HA.

Published
2015

38. Recombinant human factor VIIa (rFVIIa) in hemophilia: mode of action and evidence to date

Author

Muriel Giansily-Blaizot and Jean-François Schved

Subjects
0301 basic medicine, Reviews, 030204 cardiovascular system & hematology, Pharmacology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Tissue factor, 0302 clinical medicine, law, medicine, Platelet, Mode of action, Factor IX, Factor VII, biology, business.industry, Factor X, Hematology, 030104 developmental biology, chemistry, Recombinant factor VIIa, Recombinant DNA, biology.protein, business, medicine.drug
Abstract

Recombinant activated factor VII (rFVIIa) is a bypassing agent widely used both in the treatment and prevention of hemorrhagic complications due to hemophilia with inhibitor. In such cases, antihemophilic factors cannot be used. The normal physiology of factor VII/ factor VIIa (FVII/FVIIa) in the hemostatic process requires the presence of tissue factor (TF) that links to FVII leading to a FVIIa-TF complex which activates both factor X and factor IX. The therapeutic use of rFVIIa requires high amount of FVIIa. Some studies demonstrate that FVIIa at high doses still requires tissue factor for function, whereas others suggest that FVIIa activates FX directly on the platelet surface, in a TF-independent manner. In the present article, we discuss the arguments supporting both TF-dependent and TF-independent modes of action. Finally, the coexistence of both TF-dependent and TF-independent mechanisms cannot be excluded.

Published
2017

39. Choice of factor VIII/IX regimen in adolescents and young adults with severe or moderately severe haemophilia. A French national observational study (ORTHem 15-25)

Author

Sandrine Meunier, Roseline d'oiron, Hervé Chambost, Edita Dolimier, Benoît Guillet, Annie Borel-Derlon, Jeanne-Yvonne Borg, Ségolène Claeyssens, Roseline d'Oiron, Valérie Gay, Stéphane Girault, Jenny Goudemand, Yves Gruel, Benoit Guillet, Abel Hassoun, Philippe Nguyen, Brigitte Pautard, Jocelyne Peynet, Chantal Rothschild, Jean-François Schved, Marc Trossaert, Alain Marques-Verdier, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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), 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), Shire France, Institut de recherche en santé, environnement et travail (Irset), 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 ), Baxalta, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 )

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Haemophilia A, Hemorrhage, 030204 cardiovascular system & hematology, Hemophilia A, Haemophilia, Factor IX, Young Adult, 03 medical and health sciences, 0302 clinical medicine, On demand, Hemarthrosis, Humans, Medicine, Young adult, Retrospective Studies, Factor VIII, Coagulants, business.industry, Prophylaxis, musculoskeletal, neural, and ocular physiology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Bleed, medicine.disease, 3. Good health, Regimen, Treatment Outcome, nervous system, Haemorrhage, Female, Severe haemophilia A, Observational study, On-demand treatment, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Age groups, business, 030215 immunology
Abstract

International audience; Introduction: The value and challenges of long-term prophylaxis (LTP) in adolescents and young adults need further characterisation.Aim: To determine the proportions of adolescents and young adults with severe or moderately severe haemophilia in France under LTP and treatment on demand (OD).Methods: Patients 15 to 25 years old with haemophilia A or B, factor VIII/IX ≤ 2% and no current inhibitor could be included if they had been under factor VIII/IX treatment at least 12 months and kept a treatment and bleeding diary.Results: LTP was administered to 169/212 patients (79.7%) and OD treatment to 40/212 patients (18.9%). The most frequent reasons for initiating LTP were joint bleeding, target joints and frequent bleeds; whereas OD treatment was most often selected on the basis of mild bleeding phenotype or because of constraints on LTP. The mean annual bleed rate (ABR) in the OD group (6.33) was higher than in the LTP group (3.07, p 18–21 and > 21–25 years), but was significantly higher for patients with severe haemophilia (4.02) as compared to those with moderate haemophilia (1.97, p = 0.002). No significant difference was observed in mean ABR for joint bleeds between the LTP and OD groups. Physician reported LTP compliance was good or excellent in 97.0% of patients.Conclusion: LTP is the predominant factor VIII/IX treatment among adolescents and young adults with severe or moderately severe haemophilia in France. LTP was associated with low ABR and high compliance. © 2017 The Authors

Published
2017

40. Prise en charge des complications hémorragiques graves et de la chirurgie en urgence chez les patients recevant un anticoagulant oral anti-IIa ou anti-Xa direct. Propositions du Groupe d’intérêt en Hémostase Périopératoire (GIHP) - mars 2013

Author

E. de Maistre, P. Albaladejo, Juan V. Llau, Nadia Rosencher, Charles-Marc Samama, Anne Godier, Pierre Sié, Normand Blais, Pierre Fontana, Y. Gruel, Ariel Cohen, Jean François Schved, Patrick Mismetti, Gilles Pernod, S. Susen, and Michel Meyer Samama

Subjects
Drug, Rivaroxaban, medicine.drug_class, business.industry, media_common.quotation_subject, Anticoagulant, Atrial fibrillation, General Medicine, medicine.disease, Dabigatran, Anesthesiology and Pain Medicine, Venous thromboembolic disease, Emergency surgery, Anticoagulant therapy, Anesthesia, medicine, business, medicine.drug, media_common
Abstract

New direct oral anticoagulants (NOAC), inhibitors of factor IIa or Xa, are expected to be widely used for the treatment of venous thromboembolic disease, or in case of atrial fibrillation. Such anticoagulant treatments are known to be associated with haemorrhagic complications. Moreover, it is likely that such patients on long-term treatment with NOAC will be exposed to emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose management for optimal safety as regards the risk of bleeding in such emergency conditions. In this article, only dabigatran and rivaroxaban were discussed. For emergency surgery at risk of bleeding, we propose to dose the plasmatic concentration of drug. Levels inferior or equal to 30ng/mL for both dabigatran and rivaroxaban, should enable the realization of a high bleeding risk surgery. For higher concentration, it was proposed to postpone surgery by monitoring the evolution of the drug concentration. Action is then defined by the kind of NOAC and its concentration. If the dosage of the drug is not immediately available, proposals only based on the usual tests, PT and aPTT, also are presented. However, these tests do not really assess drug concentration or bleeding risk. In case of severe haemorrhage in a critical organ, it is proposed to reduce the effect of anticoagulant therapy using a nonspecific procoagulant drug (activated prothrombin concentrate, FEIBA, 30-50U/kg, or non-activated 4-factors prothrombin concentrates 50U/kg). For any other type of severe haemorrhage, the administration of such a procoagulant drug, potentially thrombogenic in these patients, will be discussed regarding concentration of NACO and possibilities for mechanical haemostasis.

Published
2013

41. Epidemiology - cardiovascular outcomes

Author

Eric Verbeken, Yumi Noda, Paula Specht, Angels Betriu, Ahad A. Abdalla, Bogusław Okopień, Isabelle Jaussent, Magdalena Olszanecka-Glinianowicz, MariaJose Soler, Krzysztof Labuzek, Tuan Ismail, Soo Bong Lee, Mai Sugahara, Izumi Sugimoto, Jung Eun Lee, Mohammad Ibrahim Anan, Olle Melander, Naobumi Mise, Yasuhisa Sakurai, Ailish Hannigan, Kazuko Suzuki, Cornelius J. Cronin, Isao Kubota, Harin Rhee, Nihil Chitalia, Tomokazu Okado, Amir E.L. Okely, Ludomir Stefańczyk, Masanori Emoto, Esam Lotfy Harash, Francesca Mallamaci, Magdalena Kaczmarska, Markus Ketteler, Célia Brugueirolle, Rafał Ficek, Sei Sasaki, Ghislain Opdenakker, Toshihide Naganuma, Göran Berglund, Erik Fjellstedt, Tetsuo Shoji, Jürgen Floege, Kristien Daenen, Sung Kyu Ha, Mikio Okamura, Hoon Young Choi, Hélène Leray-Moragues, Anne-Marie Dupuy, Michał Nowicki, Kenichi Ishizawa, Anna Faura, Marc Hoylaerts, Sol Otero, Tatsuya Nakatani, Il Young Kim, Astrid Weiland, Masaaki Inaba, Daniela Leonardis, Piotr Grzelak, Malaka Yehya Fouad, Inge Fourneau, Austin G. Stack, Wael Fouad Nassar, Jerzy Chudek, Byeong Yun Yang, Ilona Kurnatowska, Rika Miura, In Hye Hwang, Elvira Fernández, David Goldsmith, Jean-Paul Cristol, Hyeong Cheon Park, Bert Bammens, Julio Pascual, Hideaki Shima, Mohammad Hany Hafez, Silvia Collado, Dong Won Lee, Frances Boa, Andrzej Wiecek, Anders Christensson, Min Ji Shin, Seung Kyo Park, Kosuke Kudo, Katarzyna Wyskida, Ayako Tsuchiya, Sergi Mojal, Liam F. Casserly, Ihm Soo Kwak, Laura Tooth, Tatemitsu Rai, Eva Rodríguez, Leila Chenine, Bernard Canaud, Soichiro Iimori, Lisa Uchida, Davide Bolignano, Anna Masajtis-Zagajewska, Rocco Tripepi, Mahmoud E.L. Temraz, Marion Morena, Takafumi Kanemitsu, Muriel Giansily-Blaizot, Juan C. Kaski, Katsuhito Mori, Eiji Ishimura, Maria Andersson-Ohlsson, Nagaaki Kotera, Shinichi Uchida, Kazunobu Ichikawa, Eun Young Seong, Shinya Nakatani, Masatomo Chikamori, Kyung Nam Lee, Shotaro Naito, Tsuneo Konta, Agnieszka Zak-Gołab, Masafumi Kobayashi, Clara Barrios, Mostafa Abdelaziz Mostafa, Debasish Banerjee, Vincent Brandenburg, Hoang T. Nguyen, Tomoko Honda, Jean-François Schved, Yaser Mohammad Hendi, Kornel Pośpiech, and Carmine Zoccali

Subjects
Transplantation, medicine.medical_specialty, Nephrology, business.industry, Epidemiology, Medicine, business, Intensive care medicine, Cardiovascular outcomes
Published
2013

42. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study

Author

Odile Fremin-Batteux, Juliette Clarissou-Philippe, Benoît Jauhlac, Severine Guyetand, Jacques Gasnault, Corinne Haioun, Liamine Aissaoui, Marie-Christine Pages, Marie-Pierre Fos, Christian Rose, Didier Hubert, Marie-Rose Rothe, N. Bouziges, Benoît Huc, François Devianne, Sabine Bidart, Anne Forest, Kevin Bertrand, Mohamed Eldeghedy, Annick Verhaeghe, Caroline Malderet, Anne Bertrou, Bernard Guerquin, Catherine Duche, Muriel Archambaud, Rabea Cotteret, Olivier Toullalan, Yves Devaux, Smail Bergheul, Valérie Sivadon-Tardy, Pierre-Gilles Merville, Geneviève Blanchard-Marche, Didier Raoult, Bernard Hory, Florence Richardin, Evelyne Belle, Mohamed Menouar, K Guitteaud, Mohamad Mohty, Ambroise Montcriol, Max Laurin, Aurélia Picard, Jean-Paul Mira, Marie-Charlotte Chopin, Richard Bonnet, Michel Wolff, Sébastien Maillez, Jeanne Maugein, Véronique Leblond, Nicola Walid, Bernard Gauche, Mathieu Evillard, Hassen Jeddi, Anne Bourlet, Isabelle Grawey, Thierry Jault, Sandrine Hiret, Valerie Gaborieau, Véronique Boin-Gay, An Kim, Thierry Constans, Jean-François Gaide, Martine Giraud, Eric Meaudre Desgouttes, Alain Fur, Abdallah Maakaroun, Olivier Matray, Bertrand Maubert, Frédérique Péchinot, Aurelie Garbi, Claire Delbrouck, Benoît Grandclerc, Vincent Cadiergue, Hervé Lécuyer, Bernadette Grignon, Thierry Bensaid, Nicole Constantin, Yannick Chevalier, Hassène Rahmani, Thierry Levent, Joelle Desliers, Florence Van de Velde, Xavier Adhoute, Clara Andriau, Christophe Charasse, Rémi Vatan, Benoît Martha, Alain Lecis, Didier Albert, Romain Jacobs, Hélène Lefranc, Christian Martin, Nasseur Rezgui, Bertrand Pigeon, Catherine Le Henaff, Dominique Cassignard, Françoise Cotes, Eric Pujade Lauraine, Jean-François Gattault, Nicole Ferreira-Maident, Noémie Jourde-Chiche, Hélène Garrec, Olivier Darchen, Carole Schwebel, Marie-Christine Bezian, Patrick Daoud, Tsouria Becaid, Simone Laluque, David Broche, Christine Boisselier, Pascale Martres, Sarah Hammami, Brigitte Olivier, Jean-Marie Nkunzimana, Eric Monlun, Isabelle Marterl-Lafay, Marion Carboni, Marie-Françoise Mattei, Sandrine Castelin, Isabelle Barillot, Marie-Noelle Cufi, Thomas Kaiser, Catherine Herry, Pascal Hutin, Jean-Pierre Bronowicki, Bernard Branger, Pierre Thomas, Elie Zagdoun, Anne Goquelin, Ziad Assaf, Ingrid Croquet, Bruno Pozzetto, Thomas Similowski, Anne-Isabelle Briere, Marie-Thérèse Albertini, Mariam Blaka, Christelle Tassot, Anne Gaschet, Jean-Philippe Lavigne, Antoine Pujol, Philippe Colombat, Edouard Devaud, Hana Talabani-Boizot, François Barière, Anne-Marie Cordier, Philippe Gueudet, Georges Simon, Anne-Sophie Lipovac, Françoise Bandaly, Anne Beauplet-Lepage, Sylvie Prince, Charlotte Jouzel, Jean-Luc Deboutin, Patrick Zavadil, Louis Puybasset, Marie-Cécile Petit, Loïc Guillevin, Kamel Touati, Christophe Ntalu Nkato, Sylvie Carette, Jacques Vaucel, Chantal Delasalle, Marine Gross Goupil, Laurent Gutmann, Christiane Payen, Annick Barboteau, Firouzé Bani-Sadr, Christophe Legendre, Philippe Roulier, Elie Azria, Ibrahim Farah, Isabelle Rouquette-Vincent, Anne-Sophie Erena-Penet, Philippe Labadie, Eric Josien, Aicha Derragui, Mathieu Legrand, Odile Beyne-Rauzy, Jean-Marc Nabholtz, Marie-Joelle Demarcq, Olivier Garosi, Michel Deiber, Fabrice Chaix, Bertrand Souweine, Anne Collignon, Gisèle Renard, Mickael Jego, Gilles Bernardin, Anne Allart, Jocelyn Barrier, Marc Vasse, Philippe Ménager, Marc Wurmser, Abderkader Ouazir, Olivier Gontieron, Yvon Berland, Sébastien Trouiller, David Leysenne, Christophe Ozanon, Fanny Autret, Tahar Saghi, Loïc Dopeux, Sophie Benoit-Coustou, T. Fraisse, Christine Maillard, Karine Nikodijevic, Georges Kaltenbach, Angéline Jamet, Philippe Aucher, Julie Bottero, Marie-Claude Piffaut, Marianne Besnard, Florence Courillon, Marie Bonfils, Christine Ghevaert, Marie Destors, Eliette Jeanmaire, Franck Zerbib, Manuel-Luis Gameiro, T Prazuck, Laurent Mandin, Olivier Guisset, Marguerite Fines, Toufik Feddal, Agnès Jouffret, Louis Mesnard, Thomas Bourrée, Hasinrina Razafimahefa, Sylvestre Tigaud, Vincent Estève, Philippe Malherbe, Jean-Michel Salord, Pascal Adam, Bertrand Rozec, Michel Fuillet, Olivier Lemenand, Denis Quinsat, Ana Danalaché, Véronique Vialette, François Brosset, Patrick Messner Pellenc, Nicolas Heisel, Edouard Girard, Régine Martin, Olivier Garesslin, Catherine Mille, Alexandre Gascon, Marc Nicolino, Laurence Mouly, Claire Fabre, Bénédicte Ponceau, Marie-Etiennette Emeriau, Pascal Cathebras, Bérangère Bernardaud, Michèle Pérouse de Montclos, O. Arsene, Karine Grenet, Yazdan Yazdanpanah, Sten De Witte, Anne Scemla, Laurence Bouillet, Christophe Burucoa, Vincent Loffeier, Séverine Visentin, Luc Desfrere, Miloud Arabi, Frédérique Costa, Sylvie Lechat, Ali Chekroun, Raymond Ruimy, Marie, Jérôme Bizet, Xavier Nassif, Baihas Dib, Patrick Bert-Marcaz, Laurent Martin Lefèvre, Nicholas Sedillot, Blandine Cattier, Emilie Boidin, Daniel Sondag, Aude Bourrouillou, Alain Noirot, Franck Desemerie, Fréderic Heluwaert, Catherine Tamalet, Marc G. 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Costa, Chandrah Goburdhun, Bernard Gressier, Alban Michaud-herbst, Franck Charlier, Moussa Hecham, Luc Boulain, Hélène Corneloup, Alix Greder Belan, Nicolas Boussekey, Claire-Antoinette Dupuy, Yannick Rouquet, Benoit Renard, Benifla Jl, Etienne Javouhey, Michèle Granier, Marie-Christine Jaffarbandjee, Emilie Piet, Benoît Bergues, Claire Malbrunot, Catherine Tiry, Philippe Mérigot, Mouna Ben Soltana, Chantal Roure Sobas, Florian Radenac, Yves Thomas, Agathe Blaise, Sylvie De Martino, Laurence Legout, Gabriel Choukroun, Jean-François Muir, Peggy Dupretz, Patrick Dupont, François Guichart, Julie Jean, Jean-Michel Descamps, Bernard Kittschke, Anne Gruson, Gerard Viquesnel, Marie Keller, Pascal Chavanet, Françis Vallet, Yvan Vaschalde, Jean-Luc Hanouz, Gerard Lina, Françoise Loison, Simon Vincent, Jean-Paul Thellier, Moncef Afi, Dominique Zagozda, Hélène Sokeng-Affoule, Marc Le Bideau, Jean-François Loriferne, Alain Gravet, Sophie Deprecq, Tarik Naceur, Severine Mielczarek, René-Jean Bensadoun, Bernard Karkous, Yves Bléher, Jocelyne Poulain, Véronique Goulet, Laurence Nicolet, Sophie Arista, Antônio Lúcio Teixeira, Jean-François Schved, Laurent Nicolet, Claire Lecomte, Faiza Benddif-Fin, Michel Aumersier, Laurence Burc-Struxiano, Maxime Thouvenin, Samia Harbi, Mathieu Detave, Catherine Rebeyrotte, Jean-Paul Kisterman, Bruno Berdin, Pascal Vincent, Laurent Argaud, Elisabeth Parisi-Duchene, Geneviève Julienne, Fernanda Farto-Bensasson, Georges-Fabrice Blum, Sad Gaizi, Tali-Anne Szwebel, Raphaël Lepeule, Marie-Thérèse Climas, Anne-Françoise Dillies, Amar Boudhane, Umberto Simeoni, Pierre-François Dequin, Gérard Oliviero, Alain Gourlaouen, Caroline Piau, Marie-France Lutz-Murphy, Benoît Claude, Jean-Paul Aubry, Nadine Dubosc-Marchenay, Kamilla Chraibi, Emmanuelle Heusse, Sylvain Le Chevallier, Nathalie Brieu, Farid Sifaoui, Lorraine Letranchant, Hélène Durox, Jean-Pierre Lagasse, Adel Ghedira, Xavier Roubert, Fatma Magdoud, Hélène Jean-Pierre, Etienne Carbonelle, Olivier Dereeper, Lionel Carbillon, Christophe Billy, Mélanie Roblin, Marie-José Kodzin, Philippe Niel, Solène Makdessi, Matteo Vassallo, Maryse Archambaud, Fabian Haccourt, Didier Blaise, Stéphane Bourgeois, Elena Marcu, Charles Kubiak, Brisse Castel, François Guinet, Marie Pouzoullic, Frédérique Nathan-Bonnet, Vincent Gendrin, Céline Becherrawy, Aline Secher, Pierre Abgueguen, Clarence Eloy, Jean-Marc Tourani, Frédéric Klapczynski, Bernard Montmasson, Philippe Real, Joanna Pofelski, Yves Welker, Karim Krechiem, Eric Caumes, Martine Elena-Daumas, Christophe Saigne, Gilles Hittinger, Chantal Delesalle, Jonathan Messika, Fabrice Lesage, Daniela Pop, Daniel Coetmeur, Renato Colamarino, Chetaou Mahaza, Patrick Plésiat, Isabelle Fredenucci, Mylène Baret, Guy Mager, Pascale Chavel, Isabelle Labourdette, Anne-Claude Menguy, Nicolas Fortineau, Ludovic Le Sec, Valérie Gauduchon, Francis Barraud, Nicolas Letellier, Didier Vincent, Janine Frey, Philippe Riegel, Michel Pavic, Jean-Luc Fabre, Jean-Pierre Fauchart, Alain Goudeau, Stéphanie Husson-Wetzel, Philippe Eymerit, Mohamed Camara, Nathalie Seta, Elisabeth Carole Ngo Bell, Philippe Repellin, Laurent Alric, Vincent Leroy, Françoise Delisle Mizon, Jean-Philippe Emond, Marie-Françoise Borie, Lise Crémet, Wladimir Chelle, Elisabeth Brottier-Mancini, Bernard Garrigues, Claire Letellier, Loïc Geffray, Frédéric Méchaï, Julien Bador, Benoit Guery, Alain-Charles Fouilhoux, Corinne Dagada, Pierre Duhaut, Julien Goustille, Arnaud Sément, Francis Carcenac, Isabelle Girard-Buttaz, Claire Chapuzet, Fabienne Jouatte, Bruno Riou, Fabrice Hayoun, Chloé Di Meglio, Youssef Ali, Michel Leneveu, Nathalie Montagne, Yves Garcera, Audrey Moustache, Pierre-Eric Danin, Geneviève Le Lay, Dominique Courouge-Dorcier, Isabelle Worcel, Emmanuel Morelon, Vincent Pestre, Jean-Pierre Vilque, Jean-Christophe Paquet, Lucien Bodson, Anne-Marie Forest, Fabrice Pierre, Christian Pommier, Fabien Dutasta, Pierre Fournel, Stéphanie Courtois, Elodie Dubois, Serge Vanden Einjden, Patrick Honderlick, Pascal Richette, Fabienne Tamion, Véronique Chassy, Richard Megbemado, Anne-Marie Le Reste, Bernard Simian, Henri Osman, Anthony Texier, Badih Ayach, François Simon, Jean-Michel Filloux, Béatrice Dubourdieu, Jean-Claude Semet, Sarah Kubab, Tawfiq Henni, Patrick Dudeffant, Delphine Hequet, Olivier Mimoz, Marc Auburtin, Amélie Chabrol, Mickael Bonnan, Caroline Léonnet, Claire Wintenberger, Serge Ilunga, Patrice Lanba, Sophie Rosello, Alexandre Damage, Flore Bouche, Michel Thibault, Frederic Faibis, Chantal Dhennain, Jean-Philippe Talarmin, Armelle Lamour, Remi Boussier, Fabien Garnier, Marie-Laure Brival, Nourredine Hedjem, Philippe Vande-perre, Raphaël Coint, Jean-Claude Reveil, Eva Weinbronn, Emmanuelle Lavalard, Alexandra Fille, Françoise Le Turdu, Lionel Leroux, Jean-Yves Lefrant, Jean Berthet, Radia Bouaziz, Alain Ravaud, Sylvaine Rousseau, Yacine Merrouche, Alain Le Coustumier, Bertrand Guider, Gisèle Dewulf, Jean-Marc Faucheux, Jacques Piquet, Franck Leibinger, Charles Cerf, Robin Stephan, Jean-Philippe Redonnet, Jean-Paul Stahl, Ella Dzeing, Simona Pavel, Guy Vernet, Ghada Hatem, Samer Kayal, Jacques Deschamps, Dominique Descamps, Marion Levast, Marc Bouiller, Sylvie Dargere, Claire Dingremont, Stéphane Gaudry, François Maillot, Sylvie Odent, Nathalie Cervantes, Hélène Zanaldi, Laurence Gachassin, Olivier Ruyer, David Patin, Benoît Cazenave, Pascal Jacquier, Michelle Boyer, Béatrice Berteaux, Virginie Zarrouk, Jacques Bor, Isabelle Legoff, Hélène Albinet, Florence Rousseau, Gilles Pialoux, Guenaelle Salaun-Beretta, Alexandra Moura, Véronique Vernet Garnier, Didier Lepelletier, Pierre-Alexandre Hauss, Joëlle Belaisch-Amart, Didier Lepeletier, Jacob Xavier, Aline Nare, Annie Motard-Picheloup, Alain Améri, Bertrand Lioger, Jean-Valère Malfuson, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Médecine interne [Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie des Infections - Biology of Infection, Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Infectious Disease Department [Saint Maurice], Agence Nationale de la Santé Publique [Saint-Maurice] (ANSP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, MONALISA study group, Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency., ROZIER, marie-Claire, CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), CHU Pitié-Salpêtrière [APHP], Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections ( CNRL ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre collaborateur de l'OMS (CCOMS) des Listeria ( CCOMS ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Lariboisière, Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources ( ICAReB ), Agence Nationale de la Santé Publique [Saint-Maurice] ( ANSP ), Assistance Publique - Hôpitaux de Paris, Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)

Subjects
Bacteremia/epidemiology/mortality, 0301 basic medicine, Male, Pediatrics, bacteraemia, Infectious Disease Transmission, [SDV]Life Sciences [q-bio], Bacteremia, France/epidemiology, Infant, Newborn, Diseases, Foodborne Diseases, Meningoencephalitis, Pregnancy, Risk Factors, Vertical, Medicine, Listeriosis, Prospective Studies, Pregnancy Complications, Infectious, Prospective cohort study, ddc:618, diabetes, alcoholism, Hazard ratio, Foodborne Diseases/microbiology, immuno suppressive therapies, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Infectious Diseases, isolates, Population Surveillance, Female, France, Listeria monocytogenes/classification/isolation & purification, Cohort study, Adult, medicine.medical_specialty, 030106 microbiology, Notifiable disease, Listeriosis/diagnosis/epidemiology/microbiology, Context (language use), macromolecular substances, 03 medical and health sciences, Humans, study, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Public health, cirrhosis, Infant, Newborn, Infant, Diseases/epidemiology/microbiology, HIV, Mandatory Reporting, Newborn, medicine.disease, Listeria monocytogenes, infection, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious/epidemiology/microbiology, Meningoencephalitis/epidemiology/microbiology/mortality, Observational study, business, prognostic, mellitus
Abstract

International audience; Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (

Published
2016

43. Circulating FVIII-specific IgG, IgA and IgM memory B cells from haemophilia A patients

Author

Géraldine Lavigne-Lissalde, Isabelle Diaz, Priscilla Lapalud, Jean-Pierre Vendrell, Jean-François Schved, M Giansily-Blaizot, Edouard Tuaillon, Karine Bollore, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Traitement de l'Hémophilie, Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)

Subjects
0301 basic medicine, Immunoglobulin A, Adult, Enzyme-Linked Immunospot Assay, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, animal diseases, Haemophilia A, ELISpot, haemophilia A, 030204 cardiovascular system & hematology, Hemophilia A, Immunoglobulin G, Immune tolerance, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Immune system, hemic and lymphatic diseases, inhibitors, medicine, memory B cells, Humans, Child, Genetics (clinical), B-Lymphocytes, biology, business.industry, ELISPOT, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, medicine.disease, Flow Cytometry, Antibodies, Neutralizing, 3. Good health, 030104 developmental biology, Immunoglobulin M, factor VIII, Case-Control Studies, Immunology, biology.protein, Antibody, business
Abstract

Introduction Approximately, 25% of haemophilia A (HA) patients treated by factor VIII (FVIII), develop antibodies, known as inhibitors, neutralizing the activity of infused FVIII. This immune response involves B cells (BC), including FVIII-specific memory B cells (MBC). Production of anti-FVIII antibodies after stimulation of FVIII-specific MBC suggests a role of these cells in the immune response to FVIII. Animal models allowed the study of circulating FVIII-specific cells, however few data are available on HA patients. Aim and methods In the present study, we simultaneously detected, via ELISpot assay, different isotypes of MBC in the blood of HA patients, after polyclonal activation. Patients included: three with active inhibitors; three with a history of inhibitors; six without any past or active inhibitor. Results FVIII-specific MBC were detected in peripheral blood of HA patients: (i) patients with active inhibitors (IgG: 4–5.2/106 BC; IgA: 2.9–4/106 BC) (ii) patients with a past of inhibitors (no IgG BC; IgA: 5–7.5/106 BC) (iii) patients without inhibitors (no IgG BC or IgA BC except one patient had two FVIII-specific IgA BC/106 BC). Conclusion FVIII-specific IgA MBC were detected in HA patients with past and current immune responses against FVIII and FVIII-specific IgG MBC were found only in those with positive inhibitors. This study shows the possibility to detect and characterize easily and simultaneously the MBC from patient blood and that MBC seem different according to anti-FVIII immune history. It could be a useful tool to study anti-FVIII response and Immune Tolerance Induction cellular mechanisms.

Published
2016

44. The role of genetic factors in patients with hepatocellular carcinoma and iron overload - a prospective series of 234 patients

Author

Patricia Aguilar-Martinez, Séverine Cunat, Muriel Giansily-Blaizot, Georges-Philippe Pageaux, Natalie Funakoshi, Pierre Blanc, Jean-François Schved, Hélène Donnadieu-Rigole, Iphigénie Chaze, Michael Bismuth, Anne-Sophie Alary, Gaelle Tachon, Dominique Larrey, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Montpellier, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, and Université de Montpellier (UM)

Subjects
Male, medicine.medical_specialty, Pathology, Carcinoma, Hepatocellular, Genotype, Hepatocellular carcinoma, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepcidins, Internal medicine, Medicine, Humans, Genetic Testing, Prospective Studies, iron overload, Prospective cohort study, Hemochromatosis Protein, Cation Transport Proteins, Genetic testing, Aged, HFE mutations, Hepatology, medicine.diagnostic_test, business.industry, Transferrin saturation, Liver Neoplasms, GNPAT, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sequence Analysis, DNA, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, HAMP-153 mutation, 030220 oncology & carcinogenesis, Ferritins, Mutation, genetic factors, 030211 gastroenterology & hepatology, Female, HAMP, France, business, Liver cancer, Viral hepatitis, Acyltransferases
Abstract

Background & Aims Iron overload (IO) in HFE-related hereditary haemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC). Methods Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels ≥300 μg/L (males) or ≥200 μg/L (females) and/or transferrin saturation ≥50% (males) or ≥45% (females) had liver iron concentration (LIC) evaluated by MRI. HFE C282Y and H63D mutations were screened. Genetic analyses of genes involved in hereditary IO (HFE, HJV/HFE2, HAMP, TFR2, SLC40A1, GNPAT) were performed in patients with increased LIC. Results A total of 234 patients were included; 215 (92%) had common acquired risk factors of HCC (mainly alcoholism or chronic viral hepatitis). 119 patients had abnormal iron parameters. Twelve (5.1%) were C282Y homozygotes, three were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. Thirteen patients with a LIC>70 μmol/g were enrolled in further genetic analyses: two unrelated patients bore the HAMP:c.-153C>T mutation at the heterozygous state, which is associated with increased risk of IO and severe haemochromatosis. Specific haplotypes of SLC40A1 were also studied. Conclusions Additional genetic risk factors of IO were found in 18 patients (7.7%) among a large series of 234 HCC patients. Screening for IO and the associated at-risk genotypes in patients who have developed HCC, is useful for both determining etiologic diagnosis and enabling family screening and possibly primary prevention in relatives.

Published
2016

45. Discontinuous epitopes on the C2 domain of coagulation Factor VIII mapped by computer-designed synthetic peptides

Author

Sébastien André, Jean-François Schved, Aurélien Lebreton, Violaine Moreau, Claude Granier, Priscilla Lapalud, Christophe Nguyen, Christopher Cayzac, and Géraldine Lavigne

Subjects
chemistry.chemical_classification, congenital, hereditary, and neonatal diseases and abnormalities, biology, Chemistry, Haemophilia A, Autoantibody, Peptide, Hematology, Computational biology, medicine.disease, Virology, Epitope, Domain (software engineering), Immune system, hemic and lymphatic diseases, medicine, biology.protein, Antibody, C2 domain
Abstract

The occurrence of alloantibodies against Factor VIII (FVIII) is the main iatrogenic complication in haemophilia A (HA). Anti-FVIII autoantibodies may also spontaneously appear in non-HA patients, leading to acquired haemophilia A. In both contexts, the antibody response against FVIII is complex and difficult to analyse due to the lack of suitable tools. Our purpose was to comprehensively map, at the amino acid level, discontinuous epitopes of the C2 domain of FVIII targeted by patients' antibodies. We synthesized 33 synthetic peptides, which were predicted by the bioinformatic algorithm PEPOP to mimic C2 domain discontinuous epitopes. Using an inhibition assay based on the x-MAP technology, we evaluated their ability to block the binding to the C2 domain of anti-C2 domain antibodies from pooled plasma samples. Nine peptides were thus selected and tested again in individual plasma samples. Our results support the view that C2 domain epitopes are organized as an epitopic mosaic distributed around the molecule, showed that each patient displayed a specific anti-C2 epitopic profile, and confirmed the complexity and variability of the immune response against the C2 domain of FVIII. This ability to finely map epitopes could be further used to follow the antibody specificity modifications over time.

Published
2011

46. Prevalence and epitope specificity of non-neutralising antibodies in a large cohort of haemophilia A patients without inhibitors

Author

Priscilla Lapalud, Aurélien Lebreton, Géraldine Lavigne-Lissalde, Claude Granier, Hervé Chambost, Jean-François Schved, Claire Berger, Christophe Combescure, Pierre-Emmanuel Morange, Alain Marques-Verdier, and Christine Biron-Andreani

Subjects
Male, 0301 basic medicine, 030204 cardiovascular system & hematology, Factor VIII/immunology/metabolism, Epitope, law.invention, Epitopes, 0302 clinical medicine, law, hemic and lymphatic diseases, Prevalence, Medicine, Child, ddc:616, biology, Hematology, Middle Aged, Pathophysiology, Child, Preschool, Disease Progression, Recombinant DNA, Female, France, Antibody, Antibodies/metabolism, Adult, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Haemophilia A, Hemophilia A, Immunoglobulin light chain, Antibodies, 03 medical and health sciences, Epitopes/metabolism, Hemophilia A/epidemiology/immunology/physiopathology, Coagulopathy, Humans, Aged, Retrospective Studies, Factor VIII, Immunodominant Epitopes, business.industry, Infant, medicine.disease, 030104 developmental biology, Epitope mapping, Immunodominant Epitopes/metabolism, Immunology, biology.protein, business, Epitope Mapping
Abstract

SummaryAntibodies (inhibitors and non-neutralising antibodies [NNA]) directed against factor VIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Inhibitors reduce FVIII procoagulant properties, whereas NNA are directed against non-functional epitopes. NNA are poorly studied and their prevalence, epitope specificity and physiopathology inadequately defined. The aim of this study was first to evaluate NNA prevalence in a French retrospective multicentric series of 210 patients without inhibitors, then to determine their epitope specificity (against the heavy chain [HC] or the light chain [LC] of FVIII) and particularly to assess the prevalence of anti-B domain NNA using specifically designed x-MAP assays. NNA occurred in 18.1% of patients (38/210) and their prevalence was not influenced by the severity of the disease. Among the 38 patients with NNA, 73.7% had anti-FVIII Abs against the HC, 13.2% against the LC and 13.2% had anti-FVIII Abs against both chains. There is thus a clear immuno-dominance of the HC of FVIII in the epitope profile of NNA, whatever the severity of HA. The proportion of NNA that recognised the B domain was 18.4% (n=7/38). A multivariate analysis did not highlight differences in NNA occurrence between patients treated with recombinant FVIII or with plasma-derived FVIII (19.6% vs. 14.9%, p=0.53).

Published
2011

47. A Haut-Doubs FVII variant depending on species-derived-thromboplastin reagent (F7:p.Arg337His)

Author

C. Zawadzki, M.-A. Bertrand, Marc Trossaert, G. Mourey, Gaelle Tachon, Muriel Giansily-Blaizot, Jean-Luc Pellequer, Jean-François Schved, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire des Intéractions et Reconnaissances Moléculaires (LIRM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de Biologie Moléculaire et Centre de Pathologie (Equipe 1), INSERM-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille Nord de France (COMUE), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôtel-Dieu de Nantes, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Université Lille Nord de France (COMUE)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Thomas, Frank, and Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, Models, Molecular, medicine.medical_specialty, MESH: Mutation, Adolescent, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein Conformation, MESH: Rabbits, Thromboplastin, MESH: Protein Conformation, Species Specificity, Animals, Humans, MESH: Species Specificity, Medicine, MESH: Animals, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), MESH: Adolescent, Gynecology, MESH: Humans, MESH: Middle Aged, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, MESH: Blood Coagulation Tests, MESH: Indicators and Reagents, MESH: Adult, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Thromboplastin, Hematology, General Medicine, Factor VII, Middle Aged, MESH: Male, 3. Good health, Mutation, Female, Indicators and Reagents, Blood Coagulation Tests, Rabbits, MESH: Factor VII, business, MESH: Female, MESH: Models, Molecular
Abstract

*Laboratoire d’hemostase Etablissement Franc ais du Sang, Besanc on; †Departement d’hematologie biologique CHU deMontpellier, Hopital Saint Eloi, Montpellier;^ ‡CEA, iBEB Service de Biochimie et Toxicologie Nucleaire, Bagnols sur Ceze;§Laboratoire d’Hematologie Centre de Biologie et Pathologie EA-2693, Centre Hospitalier Regional et Universitaire, Lille;¶Centre Regional de Traitement de l’Hemophilie, Laboratoire hematologie, CHU Hotel-Dieu, Nantes; and^ kCentre Regionalde Traitement de l’Hemophilie, Service d’hematologie CHU Besanc on, Besanc on, France

Published
2014

48. Utilisation quotidienne du facteur VII activé recombinant dans les saignements aigus de l’hémophile acquise A : résultats d’ACQUI-7, une étude française prospective

Author

A. Borel-Derlon, J. Y. Borg, Hervé Levesque, Achille Aouba, Jean-François Schved, B. Villette, H. Schneid, and Benoît Guillet

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Gastroenterology, Internal Medicine
Abstract

Introduction L’efficacite et la tolerance du facteur VII active recombinant (rFVIIa) sont reconnues chez les patients avec une hemophilie A acquise (HAA), mais des donnees detaillees sur le controle du saignement en pratique medicale sont limitees. Patients et methodes L’objectif de cette etude prospective, observationnelle, multicentrique, francaise (ACQUI-7) etait de renforcer les connaissances sur les differents types de saignements survenant chez des patients HAA (titre de l’auto-anticorps anti-FVIII > 1 UB ; taux de FVIII Les donnees ont ete collectees dans 20 centres de traitement de l’hemophilie ou departement de medecine interne entre 2010 et 2013. Apres inclusion pour prise en charge d’un episode hemorragique traite par rFVIIa en 1re ou 2nde intention, les patients etaient suivis pendant 1 an. Les modalites d’utilisation du rFVIIa etaient laissees au libre arbitre de l’investigateur. Resultats Vingt-sept patients (18 hommes), âges de 76 ans (± 14 DS) ont ete recrutes. Seize (59 %) patients avaient une HAA idiopathique, les autres avaient une pathologie associee possiblement liee a la survenue de HAA (5 une polyarthrite rhumatoide, 1 un lupus erythemateux systemique, 3 une pathologie tumorale active) et/ou des medicaments potentiellement inducteurs (betalactamines [2], clopidrogel [3]). Plus de la moitie des patients avaient une maladie ou des facteurs de risque cardiovasculaires. Vingt-sept saignements (89 % severes) ont ete traites avec rFVIIa, en premiere intention. Le saignement justifiant le traitement par rFVIIa etait musculaire (12), cutane (3), digestif (3), urinaire (2), pleural (2), retroperitoneal (2), oropharynge (1), articulaire (1) et post-extraction dentaire (1). Plus de 15 jours avant l’episode hemorragique a l’origine du diagnostic, 9 patients ont presente des saignements et principalement cutanes et/ou muqueux (7). Le delai median entre le diagnostic et le traitement etait de 1,5 jour. rFVIIa etait efficace dans 89 % des saignements. La dose initiale etait de 90,5 mg/kg [83,2 ; 100,0], la duree du traitement de 4 jours [2 ; 11] avec 12 [5 ; 21] injections et la dose cumulee de 0,90 mg/kg [0,48 ; 1,79] (mediane [Q1 ; Q3]). Le nombre median quotidien d’injections pendant les 4 premiers jours etait entre 2 et 3. L’utilisation du rFVIIa pour le traitement des saignements severes entre j1 (1er jour de traitement) et j4 sont presentees dans le Tableau 1 . Au cours du traitement, une modification de la dose et/ou frequence des injections etait realisee chez 19 patients avec une augmentation chez 6 patients et une diminution chez 16 patients. Aucun evenement indesirable grave, dont evenement thromboembolique, lie au rFVIIa n’a ete rapporte. Six deces sont survenus (septicemie, saignement, deterioration generale [1] , neoplasmes [1] ). Conclusion Ces donnees sont en accord avec celles des etudes EACH2, SACHA, pour le type de saignements traites et la prise en charge globale par rFVIIa (doses cumulees, nombre total d’injections, duree de traitement). ACQUI-7 apporte des informations complementaires sur l’utilisation quotidienne du rFVIIa dans l’hemophilie acquise.

Published
2016

49. Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation - the surgical STER

Author

Alberto Dolce, Guglielmo Mariani, Jørgen Ingerslev, Jens Bjerre Knudsen, Jean François Schved, Sergio Siragusa, Günter Auerswald, M. Napolitano, and Angelika Batorova

Subjects
Excessive Bleeding, medicine.medical_specialty, Hematology, Factor VII, business.industry, medicine.medical_treatment, medicine.disease, Surgery, chemistry.chemical_compound, Dental extraction, chemistry, Internal medicine, Hemostasis, Orthopedic surgery, medicine, Coagulopathy, Prospective cohort study, business
Abstract

Excessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is a multi-centre, prospective, observational, web-based study protocol providing the frame for a structured and detailed data collection. Inhibitor occurrence was checked in a centralized fashion. Forty-one surgical operations (24 'major' and 17 'minor') were performed in 34 subjects with a carefully characterized FVII deficiency under the coverage of recombinant activated Factor VII (rFVIIa). Bleeding occurred during three major interventions of orthopaedic surgery, but rFVIIa was given at very low dose in each case. An antibody to FVII was observed in one patient who underwent a multiple dental extraction. No thromboses were reported during the 30-d follow up period. Replacement therapy with rFVIIa proved effective when suitable doses were used, which, during the period of maximum bleeding risk (the day of operation), were calculated (Receiver Operated Characteristic analysis) to be of at least 13 μg/kg/body weight per single dose and no less than three administrations. This indication is important especially in the case of major surgery.

Published
2010

50. The Management of Cardiovascular Diseases in Patients with Hemophilia: The French Coche Registry

Author

Benoît Guillet, Jean-François Schved, Aurélien Lebreton, Céline Falaise, Philippe Gautier, Ségolène Claeyssens, Bénédicte Wibaut, Guillaume Cayla, and Sabine Castet

Subjects
medicine.medical_specialty, business.industry, Immunology, Human immunodeficiency virus (HIV), Coronary arteriosclerosis, Atrial fibrillation, Cell Biology, Hematology, Overweight, medicine.disease_cause, medicine.disease, Biochemistry, Obesity, Coronary heart disease, Internal medicine, medicine, Cardiology, In patient, medicine.symptom, business, Fibrinolytic agent
Abstract

Introduction: Over the last decades, life expectancy of patients with hemophilia (PWH) has significantly improved and therefore, age-related comorbidities like cardiovascular disease (CVD) are now common features. Using antithrombotic and antiplatelet agents, as needed for managing CVD, proves complex in PWH given that these drugs, along with the often required invasive procedures, interfere with hemostasis; general recommendations are not applicable as such. Method: To collect data on current real-life practices in this patient population, the COCHE registry (COmorbidités Cardiovasculaires chez les patients HEmophiles) has been implemented back in July 2011. This French observational study sought to describe prospectively the management of CVD in PWH who require treatment with antiplatelet agents, antithrombotics, or both. Results: By January 2018, this registry had prospectively included 67 PWH: 59 hemophilia A and 8 hemophilia B patients (47 mild, 10 moderate, and 10 severe), with a median age of 65±12.5 years. Overall, 52 patients were included for coronary artery disease (CAD) and 16 for atrial fibrillation (AF), with one patient presenting both CAD and AF. Among the 67 patients enrolled, 49 were receiving on-demand replacement therapy. Identified cardiovascular risk factors were arterial hypertension (n=44), overweight or obesity (n= 35), dyslipidemia (n=30; four tested positive for human immune deficiency virus [HIV]), smoking (n=17), family coronary disease history (n=11), non-insulin dependent diabetes mellitus (NIDDM) (n=11), and insulin dependent diabetes mellitus (IDDM) (n=3). Conclusion: The proposals discussed herein are largely based on the experience we gained whilst managing PWH with CVD from the COCHE registry. To us, a multidisciplinary approach appears paramount. Disclosures Lebreton: Sobi: Consultancy, Research Funding.

Published
2018

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