Siguret-Depasse Virginie

PU-PH, AP-HP

Research theme : Theme 2 – Part 2

Phone: 01 53 73 15 57
01 49 95 63 95

Biography

Notre principale thématique de recherche, porte sur la pharmacologie et la pharmacogénétique des traitements antithrombotiques, la variabilité de réponse à ces traitements, la compréhension des mécanismes responsables de cette variabilité et l’amélioration de la prise en charge des patients à risque.

Pour exemple, plus de 2 millions de patients reçoivent un traitement anticoagulant chaque année en France, et ces médicaments sont la première cause de iatrogénie médicamenteuse. Nous menons aussi bien des études de pharmacocinétique/pharmacodynamique chez le volontaire sain que des études cliniques cliniques multicentriques de phase IV dans des cohortes de patients «particuliers» (patients très âgés,  insuffisants rénaux, enfants).

Nous conduisons également des travaux plus fondamentaux in-vitro sur les mécanismes d’action et la réversion des antithrombotiques. En particulier, nos objectifs visent à l’aide de modèles, à mieux comprendre les causes génétiques (polymorphismes de gènes impliqués dans le transport et le métabolisme des antithrombotiques) et non génétiques (âge avancé, comorbidités, médicaments associés) impliquées dans la variabilité de la réponse aux dérivés hépariniques, aux anti-vitamines K (AVK) et aux anticoagulants oraux directs (dabigatran étexilate, rivaroxaban, apixaban, edoxaban).

Major publications 2020 / 2010

Tinzaparin Sodium Pharmacokinetics in Patients with Chronic Kidney Disease: Practical Implications. Hélène Helfer, Virginie Siguret, Isabelle Mahé – 2020 Jun – PMID: 31721053 PMCID: PMC7266849 DOI: 10.1007/s40256-019-00382-0

Potential usefulness of activated charcoal (DOAC remove®) for dRVVT testing in patients receiving Direct Oral AntiCoagulants. Georges Jourdi, Maxime Delrue, Alain Stepanian, Jessica Valaize, Geoffrey Foulon-Pinto, Julien Demagny, Jerome Duchemin, Fabienne Nedelec-Gac, Luc Darnige, Emmanuel Curis, Xavier Delavenne, Pascale Gaussem, Virginie Siguret, Isabelle Gouin-Thibault – 2019 Dec – PMID: 31710863 DOI: 10.1016/j.thromres.2019.11.001

International Council for Standardization in Haematology Recommendations for Hemostasis Critical Values, Tests, and Reporting. Robert C Gosselin, Dorothy Adcock, Akbar Dorgalaleh, Emmanuel J Favaloro, Giuseppe Lippi, João M Pego, Irene Regan, Virginie Siguret – 2020 Jun – PMID: 31639855 DOI: 10.1055/s-0039-1697677

Pain assessment and factors influencing pain during bone marrow aspiration: A prospective study. Nicolas Gendron, Sara Zia Chahabi, Géraldine Poenou, Nadia Rivet, Tiphaine Belleville-Rolland, Pierre Lemaire, Antoine Escuret, Michèle Ciaudo, Emmanuel Curis, Pascale Gaussem, Virginie Siguret, Luc Darnige – 2019 Aug 29 – PMID: 31465426 PMCID: PMC6715342 DOI: 10.1371/journal.pone.0221534

Rivaroxaban pharmacodynamics in healthy volunteers evaluated with thrombin generation and the active protein C system: modeling and assessing inter-individual variability. Siguret V, Abdoul J, Delavenne X, Curis E, Carlo A, Blanchard A, Salem JE, Gaussem P, Funck-Brentano C, Azizi M, Mismetti P, Loriot MA, Lecompte T, Gouin-Thibault I. J Thromb Haemost. 2019 Jun 19. doi: 10.1111/jth.14541.

Multifactorial hypercoagulable state associated with a thrombotic phenotype in phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG): Case report and brief review of the literature. Lefrère B, Stepanian A, Charles P, Foulon-Pinto G, Béranger N, Alhenc-Gelas M, Drouet L, Siguret V. Thromb Res. 2019 Jun;178:75-78. doi: 10.1016/j.thromres.2019.04.010.

[Von Willebrand disease in the elderly]. Itzhar-Baïkian N, Veyradier A, Dillinger JG, Stepanian A, Pautas É, Siguret V. Rev Prat. 2018 Dec;68(10):1125-1131.

Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals. Danese E, Raimondi S, Montagnana M, Tagetti A, Langaee T, Borgiani P, Ciccacci C, Carcas AJ, Borobia AM, Tong HY, Dávila-Fajardo C, Rodrigues Botton M, Bourgeois S, Deloukas P, Caldwell MD, Burmester JK, Berg RL, Cavallari LH, Drozda K, Huang M, Zhao LZ, Cen HJ, Gonzalez-Conejero R, Roldan V, Nakamura Y, Mushiroda T, Gong IY, Kim RB, Hirai K, Itoh K, Isaza C, Beltrán L, Jiménez-Varo E, Cañadas-Garre M, Giontella A, Kringen MK, Haug KBF, Gwak HS, Lee KE, Minuz P, Lee MTM, Lubitz SA, Scott S, Mazzaccara C, Sacchetti L, Genç E, Özer M, Pathare A, Krishnamoorthy R, Paldi A, Siguret V, Loriot MA, Kutala VK, Suarez-Kurtz G, Perini J, Denny JC, Ramirez AH, Mittal B, Rathore SS, Sagreiya H, Altman R, Shahin MHA, Khalifa SI, Limdi NA, Rivers C, Shendre A, Dillon C, Suriapranata IM, Zhou HH, Tan SL, Tatarunas V, Lesauskaite V, Zhang Y, Maitland-van der Zee AH, Verhoef TI, de Boer A, Taljaard M, Zambon CF, Pengo V, Zhang JE, Pirmohamed M, Johnson JA, Fava C. Clin Pharmacol Ther. 2019 Jun;105(6):1477-1491. doi: 10.1002/cpt.1323.

Modified ROTEM for the detection of rivaroxaban and apixaban anticoagulant activity in whole blood: A diagnostic test study. Pailleret C, Jourdi G, Siguret V, Gouin-Thibault I, Gandrille S, Stepanian A, Curis E, Golmard JL, Gaussem P, Le Bonniec B, Samama CM. Eur J Anaesthesiol. 2019 Jun;36(6):449-456. doi: 10.1097/EJA.0000000000000903.

FXa-α2-Macroglobulin Complex Neutralizes Direct Oral Anticoagulants Targeting FXa In Vitro and In Vivo. Jourdi G, Gouin-Thibault I, Siguret V, Gandrille S, Gaussem P, Le Bonniec B. Thromb Haemost. 2018 Sep;118(9):1535-1544. doi: 10.1055/s-0038-1667014.

Erratum to “Thrombin generation test: A reliable tool to evaluate the pharmacodynamics of vitamin K antagonist rodenticides in rats” [Pestic. Biochem. Physiol. 146 (2018) 19-24]. Jourdi G, Lefèbvre S, Le Bonniec B, Curis E, Gaussem P, Lattard V, Siguret V. Pestic Biochem Physiol. 2018 Jul;149:149. doi: 10.1016/j.pestbp.2018.05.003.

Thrombin generation test: A reliable tool to evaluate the pharmacodynamics of vitamin K antagonist rodenticides in rats. Jourdi G, Lefèbvre S, Le Bonniec B, Curis E, Gaussem P, Lattard V, Siguret V. Pestic Biochem Physiol. 2018 Apr;146:19-24. doi: 10.1016/j.pestbp.2018.02.004. Epub 2018 Feb 15. Erratum in: Pestic Biochem Physiol. 2018 Jul;149:149. Georges, Jourdi [corrected to Jourdi, Georges]; Sebastien, Lefèbvre [corrected to Lefèbvre, Sebastien]; Bernard, Le Bonniec [corrected to Le Bonniec, Bernard]; Emmanuel, Curis [corrected to Curis, Emmanuel]; Pascale, Gaussem [corrected to Gaussem, Pascale].

Vitamin K antagonists and emergencies. Lapostolle F, Siguret V, Martin AC, Pailleret C, Vigué B, Zerbib Y, Tazarourte K. Eur J Emerg Med. 2018 Dec;25(6):378-386. doi: 10.1097/MEJ.0000000000000541. Review.

Are Screening Tests Reliable to Rule Out Direct Oral Anticoagulant Plasma Levels at Various Thresholds (30, 50, or 100 ng/mL) in Emergency Situations? Jabet A, Stepanian A, Golmard JL, Flaujac C, Joly BS, Gouin-Thibault I, Siguret V. Chest. 2018 Jan;153(1):288-290. doi: 10.1016/j.chest.2017.09.047.

Bleeding risk of antiplatelet drugs compared with oral anticoagulants in older patients with atrial fibrillation: a systematic review and meta-analysis. Melkonian M, Jarzebowski W, Pautas E, Siguret V, Belmin J, Lafuente-Lafuente C. J Thromb Haemost. 2017 Jul;15(7):1500-1510. doi: 10.1111/jth.13697

Interindividual variability in dabigatran and rivaroxaban exposure: contribution of ABCB1 genetic polymorphisms and interaction with clarithromycin. Gouin-Thibault I, Delavenne X, Blanchard A, Siguret V, Salem JE, Narjoz C, Gaussem P, Beaune P, Funck-Brentano C, Azizi M, Mismetti P, Loriot MA. J Thromb Haemost. 2017 Feb;15(2):273-283. doi: 10.1111/jth.13577

A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease: A New Epidemiologic Picture. Veyradier A, Boisseau P, Fressinaud E, Caron C, Ternisien C, Giraud M, Zawadzki C, Trossaert M, Itzhar-Baïkian N, Dreyfus M, d’Oiron R, Borel-Derlon A, Susen S, Bezieau S, Denis CV, Goudemand J; French Reference Center for von Willebrand disease. Medicine (Baltimore). 2016 Mar;95(11):e3038. doi: 10.1097/MD.0000000000003038.

Myelodysplastic syndromes with single neutropenia or thrombocytopenia are rarely refractory cytopenias with unilineage dysplasia by World Health Organization 2008 criteria and have favourable prognosis. Gyan E, Andrieu V, Sanna A, Caille A, Schemenau J, Sudaka I, Siguret V, Malet M, Park S, Bordessoule D, Mairesse J, Gelsi-Boyer V, Cheze S, Beyne-Rauzy O, Sébert M, Sapena R, Zerazhi H, Legros L, Guerci-Bresler A, Amé SN, Germing U, Santini V, Salvi F, Gioia D, Lunghi M, Dreyfus F, Fenaux P; Groupe Francophone des Myélodysplasies, Fondazione Italiana per le Sindromi Mielodisplastiche (FISMonlus), and Düsseldorf MDS Registry. Br J Haematol. 2016 Dec;175(5):975-979. doi: 10.1111/bjh.13902.

Association rate constants rationalise the pharmacodynamics of apixaban and rivaroxaban. Jourdi G, Siguret V, Martin AC, Golmard JL, Godier A, Samama CM, Gaussem P, Gouin-Thibault I, Le Bonniec B. Thromb Haemost. 2015 Jul;114(1):78-86. doi: 10.1160/TH14-10-0877.

Prevalence of Hereditary Thrombophilia in Patients Older Than 75 Years With Venous Thromboembolism Referred for Thrombophilia Screening. Siguret V, Emmerich J, Belleville T, Golmard JL, Mazoyer E, Gouin-Thibault I, Pautas E. J Gerontol A Biol Sci Med Sci. 2015 Aug;70(8):977-81. doi: 10.1093/gerona/glu240.

Multimodal assessment of non-specific hemostatic agents for apixaban reversal. Martin AC, Gouin-Thibault I, Siguret V, Mordohay A, Samama CM, Gaussem P, Le Bonniec B, Godier A. J Thromb Haemost. 2015 Mar;13(3):426-36. doi: 10.1111/jth.12830.

[Determination of full blood count normal reference values for adults in France]. Troussard X, Vol S, Cornet E, Bardet V, Couaillac JP, Fossat C, Luce JC, Maldonado E, Siguret V, Tichet J, Lantieri O, Corberand J; Groupe francophone d’hématologie cellulaire (GFHC). Ann Biol Clin (Paris). 2014 Sep-Oct;72(5):561-81. doi: 10.1684/abc.2014.0979.

[Evaluation of the impact of a training program on vitamin K antagonists (VKA) implemented by pharmacy students aiming at improving the knowledge of patients receiving vitamin K antagonists during their hospital clinical training course]. Conort O, Siguret V, Bourdon O, Nazaraly S, Brignone M, Pons-Kerjean N, Houze S, Laribe Cage S, Berthet F, Golmard JL, Brion F, Tilleul P. Ann Pharm Fr. 2014 Jul;72(4):287-95. doi: 10.1016/j.pharma.2014.02.004.

Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Noris P, Schlegel N, Klersy C, Heller PG, Civaschi E, Pujol-Moix N, Fabris F, Favier R, Gresele P, Latger-Cannard V, Cuker A, Nurden P, Greinacher A, Cattaneo M, De Candia E, Pecci A, Hurtaud-Roux MF, Glembotsky AC, Muñiz-Diaz E, Randi ML, Trillot N, Bury L, Lecompte T, Marconi C, Savoia A, Balduini CL, Bayart S, Bauters A, Benabdallah-Guedira S, Boehlen F, Borg JY, Bottega R, Bussel J, De Rocco D, de Maistre E, Faleschini M, Falcinelli E, Ferrari S, Ferster A, Fierro T, Fleury D, Fontana P, James C, Lanza F, Le Cam Duchez V, Loffredo G, Magini P, Martin-Coignard D, Menard F, Mercier S, Mezzasoma A, Minuz P, Nichele I, Notarangelo LD, Pippucci T, Podda GM, Pouymayou C, Rigouzzo A, Royer B, Sie P, Siguret V, Trichet C, Tucci A, Saposnik B, Veneri D; European Hematology Association – Scientific Working Group on Thrombocytopenias and Platelet Function Disorders. Haematologica. 2014 Aug;99(8):1387-94. doi: 10.3324/haematol.2014.105924.

[Management of vitamin K antagonists in the elderly]. Belleville T, Pautas É, Gaussem P, Siguret V. Ann Biol Clin (Paris). 2014 Mar-Apr;72(2):185-92. doi: 10.1684/abc.2014.0933. Review.

[Relationship between maintenance dosages of fluindione (Préviscan) and warfarin (Coumadin) for patients 70 years and older]. Pautas É, Peyron I, Gouin-Thibault I, Gouronnec A, Monti A, Bouhadiba S, Badie C, Golmard JL, Siguret V. Rev Med Interne. 2015 Jan;36(1):7-9. doi: 10.1016/j.revmed.2013.11.017.

Accreditation of automated complete blood count by the LH750 Analyzer (Beckman Coulter) in Georges Pompidou Hospital (Paris, France)]. Robinet S, Lemaire P, Louis G, Vieillefond V, Daigneau Y, Gaillaud E, Vincent B, Fischer AM, Siguret V. nn Biol Clin (Paris). 2013 Nov-Dec;71(6):717-30. doi: 10.1684/abc.2013.0892.

A model predicting fluindione dose requirement in elderly inpatients including genotypes, body weight, and amiodarone. Moreau C, Pautas E, Duverlie C, Berndt C, Andro M, Mahé I, Emmerich J, Lacut K, Le Gal G, Peyron I, Gouin-Thibault I, Golmard JL, Loriot MA, Siguret V. Thromb Haemost. 2014 Apr 1;111(4):705-12. doi: 10.1160/TH13-07-0555.

Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study. Gouin-Thibault I, Flaujac C, Delavenne X, Quenet S, Horellou MH, Laporte S, Siguret V, Lecompte T. Thromb Haemost. 2014 Feb;111(2):240-8. doi: 10.1160/TH13-06-0470.

Full blood count normal reference values for adults in France. Troussard X, Vol S, Cornet E, Bardet V, Couaillac JP, Fossat C, Luce JC, Maldonado E, Siguret V, Tichet J, Lantieri O, Corberand J; French-Speaking Cellular Hematology Group (Groupe Francophone d’Hématologie Cellulaire, GFHC). J Clin Pathol. 2014 Apr;67(4):341-4. doi: 10.1136/jclinpath-2013-201687.

Optimizing the use of anticoagulants (heparins and oral anticoagulants) in the elderly. Siguret V, Gouin-Thibault I, Gaussem P, Pautas E. Drugs Aging. 2013 Sep;30(9):687-99. doi: 10.1007/s40266-013-0101-0. Review.

Anticoagulant clinics are they effective in France? Performance evaluation of six anticoagulant clinics concerning the management of vitamin K antagonists]. Cambus JP, Magnin D, Ambid-Lacombe C, Bura A, Desgrippes F, Schneller JM, Benhamou Y, Flaujac C, Horellou MH, De Raucourt E, Kaczan D, Astoul M, Siguret V. Rev Med Interne. 2013 Sep;34(9):515-21. doi: 10.1016/j.revmed.2013.02.001

Genetic resistance to warfarin therapy masked by amiodarone in a 2-year-old girl with mitral valve replacement. Moreau C, Bajolle F, Siguret V, Loriot MA, Bonnet D. J Thromb Haemost. 2013 Mar;11(3):555-72. doi: 10.1111/jth.12105.

Anemia in the elderly: usefulness of an easy and comprehensive laboratory screen. Pautas E, Siguret V, Kim TM, Chaïbi P, Golmard JL, Gouronnec A, Nivet-Antoine V, Gouin-Thibault I. Ann Biol Clin (Paris). 2012 Nov-Dec;70(6):643-7. doi: 10.1684/abc.2012.0746.

Impact of the CYP4F2 p.V433M polymorphism on coumarin dose requirement: systematic review and meta-analysis. Danese E, Montagnana M, Johnson JA, Rettie AE, Zambon CF, Lubitz SA, Suarez-Kurtz G, Cavallari LH, Zhao L, Huang M, Nakamura Y, Mushiroda T, Kringen MK, Borgiani P, Ciccacci C, Au NT, Langaee T, Siguret V, Loriot MA, Sagreiya H, Altman RB, Shahin MH, Scott SA, Khalifa SI, Chowbay B, Suriapranata IM, Teichert M, Stricker BH, Taljaard M, Botton MR, Zhang JE, Pirmohamed M, Zhang X, Carlquist JF, Horne BD, Lee MT, Pengo V, Guidi GC, Minuz P, Fava C. Clin Pharmacol Ther. 2012 Dec;92(6):746-56. doi: 10.1038/clpt.2012.184.

[Vitamin K antagonists: from discovery to pharmacogenetics]. Moreau C, Loriot MA, Siguret V. Ann Biol Clin (Paris). 2012 Oct 1;70(5):539-51. doi: 10.1684/abc.2012.0740. Review. French.

Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients. Smires FZ, Moreau C, Habbal R, Siguret V, Fadili S, Golmard JL, Assaidi A, Beaune P, Loriot MA, Nadifi S. J Clin Pharm Ther. 2012 Oct;37(5):594-8. doi: 10.1111/j.1365-2710.2012.01340.x.

Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement. Moreau C, Bajolle F, Siguret V, Lasne D, Golmard JL, Elie C, Beaune P, Cheurfi R, Bonnet D, Loriot MA. Blood. 2012 Jan 19;119(3):861-7. doi: 10.1182/blood-2011-07-365502.

No accumulation of the peak anti-factor Xa activity of tinzaparin in elderly patients with moderate-to-severe renal impairment: the IRIS substudy. Siguret V, Gouin-Thibault I, Pautas E, Leizorovicz A. J Thromb Haemost. 2011 Oct;9(10):1966-72. doi: 10.1111/j.1538-7836.2011.04458.x.

[Management of complications with antivitamin K in elderly people]. Pautas E, Mitha N, Gouronnec A, Siguret V, Gouin-Thibault I. Soins Gerontol. 2011 May-Jun;(89):12-6. French.

[Divisibility of warfarin and fluindione tablets tested in elderly patients and their family circle]. Pautas E, Despres J, Peyron I, Golmard JL, Grange J, Koenig N, Gouronnec A, Mitha N, Siguret V, Gouin-Thibault I. Geriatr Psychol Neuropsychiatr Vieil. 2011 Jun;9(2):171-7. doi: 10.1684/pnv.2011.0269.

[Hodgkin lymphoma in the elderly]. Belleville T, Bouhadiba S, Fontaine J, Gouin-Thibault I, Gouronnec A, Le Tourneau A, Monti A, Pautas E, Siguret V. Ann Biol Clin (Paris). 2011 May-Jun;69(3):319-24. doi: 10.1684/abc.2011.0529. French.

Reversal of overanticoagulation in very elderly hospitalized patients with an INR above 5.0: 24-hour INR response after vitamin K administration. Pautas E, Peyron I, Bouhadiba S, Golmard JL, Gouronnec A, Oboa N, Siguret V, Gouin-Thibault I. Am J Med. 2011 Jun;124(6):527-33. doi: 10.1016/j.amjmed.2011.01.016.

Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep® in Renal Insufficiency Study (IRIS). Leizorovicz A, Siguret V, Mottier D; Innohep® in Renal Insufficiency Study Steering Committee, Leizorovicz A, Siguret V, Mottier D, Clonier F, Janas M, Stinson J, Townshend G, Maddalena M. Thromb Res. 2011 Jul;128(1):27-34. doi: 10.1016/j.thromres.2011.03.002.

Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes. oreau C, Pautas E, Gouin-Thibault I, Golmard JL, Mahé I, Mulot C, Loriot MA, Siguret V. J Thromb Haemost. 2011 Apr;9(4):711-8. doi: 10.1111/j.1538-7836.2011.04213.x.

[Screening for thrombophilic abnormalities in very elderly patients]. Anard-Michelot H, Siguret V, Gouin-Thibault I, Siriwardana M, Gouronnec A, Pautas E. Ann Biol Clin (Paris). 2010 Nov-Dec;68(6):643-8. doi: 10.1684/abc.2010.0484. French.

Human NK cells display major phenotypic and functional changes over the life span. Le Garff-Tavernier M, Béziat V, Decocq J, Siguret V, Gandjbakhch F, Pautas E, Debré P, Merle-Beral H, Vieillard V. Aging Cell. 2010 Aug;9(4):527-35. doi: 10.1111/j.1474-9726.2010.00584.x.