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Investigation of the pathophysiological aspects and novel therapeutic approaches for thromboembolic disorders

Grant number: 16/14172-6
Support type:Research Projects - Thematic Grants
Duration: May 01, 2017 - April 30, 2022
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Joyce Maria Annichino-Bizzacchi
Grantee:Joyce Maria Annichino-Bizzacchi
Home Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Principal researchers:Erich Vinicius de Paula ; Fernanda Loureiro de Andrade Orsi ; Katia Borgia Barbosa Pagnano
Assoc. researchers: Beatriz de Moraes Martinelli ; Bruna de Moraes Mazetto Fonseca ; Carmen Silvia Passos Lima ; Carolina Mie Kawagosi Onodera ; Claudio Alberto Torres Suazo ; Fábio Hüsemann Menezes ; Fernanda Dutra Santiago Bassora ; Gerson Jhonatan Rodrigues ; Isabella Macedo Toni ; José Barreto Campello Carvalheira ; Kiara Cristina Senger Zapponi Cerri ; Letícia Queiroz da Silva ; Ljubica Tasic ; Luis Fernando Bittar Sckayer ; Maurício Etchebehere ; Melissa Quintero Escobar ; Nelson Adami Andreollo ; Nelson Wolosker ; Patricia Moriel ; Rubens Maciel Filho ; Silmara Aparecida de Lima Montalvão ; Simone Appenzeller ; Stephany Cares Huber ; Suely Meireles Rezende ; Tayana Bezerra Teixeira Mello ; Tiago Dias Martins ; Vitória Régia Pereira Pinheiro ; Wagner José Fávaro
Associated grant(s):20/05985-9 - Evaluation of the mechanisms of hemostatic activation in COVID-19 and their modulation by bradykinin inhibitors, AP.R
19/23552-5 - Vasoreparative processes in the pathogenesis of deep vein thrombosis (DVT), AP.R SPRINT
18/02589-5 - EMU granted in process 2016 / 14172-6 - 02 gene rotors Q5plex-HRM platform - Quiagen brand, AP.EMU
17/15021-4 - Multi user equipament granted in process 2016/14172-6: automated optical microscopy for phase contrast system and dual color fluorescence, model incucyte zoom HD/2 channel, Essen Bioscience (exclusivity), AP.EMU
Associated scholarship(s):21/02831-3 - Epidemiology of venous thromboembolism in childhood and adolescence: disease registration in a Brazilian population, BP.TT
21/02824-7 - ASSESSMENT OF RISK FACTORS FOR DEEP VENOUS THROMBOSIS IN CANCER PATIENTS., BP.TT
21/02830-7 - Evaluation of the activity of circulating colony forming endothelial cells (ECFCs) in patients with spontaneous and induced venous thrombosis., BP.TT
+ associated scholarships 20/16105-0 - Characterization of the thromboembolic risk in COVID-19, BP.IC
20/15499-4 - Epidemiology of venous thromboembolism in childhood and adolescence: disease registration in a Brazilian population, BP.TT
19/20136-0 - Evaluation of signature of genes related to thromboty diseases in antiphospholipid syndrome, BP.MS
20/06156-6 - Importance of antiphospholipid antibodies of the IgA class for the prognosis of antiphospholipid syndrome, BP.IC
20/08990-3 - Assessment of risk factors for deep venous thrombosis in cancer patients, BP.TT
19/20320-6 - Role of extracellular vesicles as markers of inflammation and adverse clinical outcomes in orthotopic liver transplantation, BP.MS
19/20891-3 - Characterization of plasmacytoid dendritic cell activity and type 1 interferon signature in primary antiphospholipid syndrome with thrombosis, BP.MS
19/18195-9 - New methodologies for assessing coagulation activation and endothelial barrier integrity, BP.TT
19/06318-9 - Thrombosis and Inflammation: Participation of innate immunity and NETosis in the pathogenesis of hypercoagulability in chronic myeloproliferative, BP.TT
18/15618-3 - Evaluation of the activity of circulating colony forming endothelial cells (ECFCs) in patients with spontaneous and induced Venous Thrombosis, BP.DR
18/24577-9 - The role of tissue factor in APS hypercoagulability, BP.TT
18/18624-4 - Metabolomic and metabonomic analyzes by nuclear magnetic resonance techniques applied in studies of venous thrombosis, BP.PD
18/20440-9 - Evaluation of risk factors for venous thromboembolism in cancer patients, BP.TT
18/10602-1 - Preditive factors of recurrent venous thromboembolism using design of experiments, BP.IC
18/14349-9 - Thrombosis and inflammation: participation of innate immunity and NETosis in the pathogenesis of hypercoagulability in chronic myeloproliferative diseases, BP.TT
18/11308-0 - The role of tissue factor in hypercoagulability of the SAF, BP.TT
17/19251-4 - MicroRNAs and oxidized biomolecules as possible biomarkers of primary antiphospholipid syndrome, BP.MS - associated scholarships

Abstract

Thromboembolic disorders represent a major culprit for morbidity-mortality in Brazil and the World. The Hemocentro at Unicamp has a scientifically recognized research group, with over 100 highly cited publications in this field. We have revealed the roles of FVIII, VWF and of ADAMTS13 in Deep Venous Thrombosis (DVT) and severe Post-Thrombotic Syndrome (PTS); the association between hypercoagulability, inflammation and neutrophils; circulating endothelial cells and repairing processes; protein expression in venous thrombus in animals exposed arterial risk factors; platelet proteins differentially expressed and in vitro studies supporting these results. Analyze the images of residual thrombi using the Grayscale Median (GSM) suggested clinical applicability for rethrombosis. We have demonstrated immature platelet fraction and generation of thrombin in acute inflammatory process such as sepsis and SIRS. We investigated gene therapy using VEGF in peripheral arterial occlusive model in rats, and we are evaluating fat stromal cells or Platelet Rich Plasma (PRP) in murine models. All these studies demonstrated that many issues remain open and the continuity of our investigations. Hemocentro at Unicamp has a bioterium with models for arterial and vein thrombosis, imaging methods like laser doppler perfusion imager and doppler ultrasound, and transgenic models available at the animal facility center of the University, CEMIB. Our outpatient clinic has over 500 patients followed for 5 years, and patients diagnosed with DVT at the Unicamp Hospital School are currently referred to our service. Patients with Antiphospholipid Syndrome and thrombotic manifestations constitute a fruitful cohort for investigation. In this thematic project, the focus will be maintained on the pathophysiological mechanisms in DVT and investigation of novel therapies to the prevention of atherosclerosis and treatment of peripheral arterial disease. The collaboration established with the professors of renowned research groups (Paolo Simmioni, University of Padua, Italy; Leonardo Brandão, Hospital for Sick Children, Toronto, Canadá; Ricardo Forastieiro, Favaloro University, Buenos Aires, Argentina; Jose Diaz, University of Michigan, Ann Arbor, EUA) will be of great support for the development of cutting-edge research. Our research strategy will be divided into five main branches: 1) DVT - Evaluate Neutrophil Extracellular Traps (NETs), hypercoagulability and inflammation correlating them with the development of PTS and recurrence. Analyze prospectively residual thrombi using GSM and validate their association with rethrombosis. Determine DVT prevalence in a pediatric registry. Analyse mathematically DVT recurrence using artificial neural nets and fuzzy logic. Investigate the endothelium contribution to DVT development; 2) Cancer - Explore NETs in patients with Polycythemia Vera and Essential Thrombocythemia. Evaluate the mechanisms associated to cardiovascular events in patients with Chronic Myeloid Leukemia treated with tyrosine kinase inhibitor. Investigate in a Brazilian multicenter study DVT risk factors in cancer patients; 3) Antiphospholipid Syndrome - Evaluate the pathophysiology of thrombotic events, risk factors and novel therapeutic approaches; 4) Inflammation and thrombosis - explore the association between inflammation and hemostasis activation, focusing the interfaces between innate immune system and hypercoagulability of acute and chronic disorders; 5) Novel therapeutic approaches - evaluate PRP upon angiogenesis in patients with Peripheral Arterial Occlusive Disease (PAOD); PRP and Mesenchymal Cells (MSCs), in the healing process of ulcers in animal models; the use of low doses of rivaroxaban and dabigatran and development of atherosclerosis in LDL or apoE deficient murine model. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Una plataforma digital reúne genes de referencia para la investigación biomolecular 
Online platform offers reference gene database for biomolecular research 
Plataforma on-line reúne genes de referência para pesquisa biomolecular 
Articles published in other media outlets (6 total):
More itemsLess items
UNICAMP - Universidade Estadual de Campinas: Plataforma on-line reúne genes de referência para pesquisa de biomolecular (04/Dec/2020)
LabNetwork: Plataforma on-line reúne genes de referência para pesquisa biomolecular (26/Nov/2020)
Plantão News (MT): Plataforma on-line reúne genes de referência para pesquisa biomolecular (25/Nov/2020)
Jornal da Ciência online: Plataforma on-line reúne genes de referência para pesquisa biomolecular (24/Nov/2020)
Biblioteca FMUSP: Plataforma on-line reúne genes de referência para pesquisa biomolecular (24/Nov/2020)
ABIPTI - Associação Brasileira das Instituições de Pesquisa Tecnológica e Inovação: Plataforma on-line reúne genes de referência para pesquisa biomolecular (24/Nov/2020)

Scientific publications (15)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VAZ, CAMILA O.; MAZETTO, BRUNA M.; VASCONCELOS, PEDRO EDUARDO N. S.; BASTOS, LARISSA B.; CURSINO, MARIA APARECIDA; FRANCA QUINTANILHA, JULIA COELHO; TRIPIQUIA VECHIATTO MESQUITA, GABRIELA LISIANE; SANTOS, ANA PAULA R.; JACINTHO, BRUNA CARDOSO; OLIVEIRA, JOSE DIOGO; ANNICHINO-BIZZACHI, JOYCE; ORSI, FERNANDA A. Association between plasmatic oxidative stress and thrombosis in primary antiphospholipid syndrome. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, JUL 2021. Web of Science Citations: 0.
VAZ, CAMILA DE OLIVEIRA; MAZETTO FONSECA, BRUNA DE MORAES; NASCIMENTO SILVA VASCONCELOS, PEDRO EDUARDO; BASTOS, LARISSA BRITO; CURSINO, MARIA APARECIDA; FRANCA QUINTANILHA, JULIA COELHO; TRIPIQUIA VECHIATTO MESQUITA, GABRIELA LISIANE; ROSA DOS SANTOS, ANA PAULA; JACINTHO, BRUNA CARDOSO; OLIVEIRA, JOSE DIOGO; ANNICHINO-BIZZACHI, JOYCE; ORSI, FERNANDA ANDRADE. Self-perceived quality of life of primary antiphospholipid syndrome patients using vitamin K antagonist. Lupus, v. 30, n. 5, p. 707-714, APR 2021. Web of Science Citations: 0.
DA SILVA, LETICIA QUEIROZ; CANCELA, REBECA BRITO BONANI; DE LIMA MONTALVAO, SILMARA APARECIDA; HUBER, STEPHANY CARES; VIEIRA-DAMIANI, GISLAINE; TRIGLIA, RENATA MARCHI; ANNICHINO-BIZZACCHI, JOYCE MARIA. The effect of lyophilized platelet rich-plasma on skin aging: a non-randomized, controlled, pilot trial. ARCHIVES OF DERMATOLOGICAL RESEARCH, FEB 2021. Web of Science Citations: 0.
HOUNKPE, BIDOSSESSI WILFRIED; CHENOU, FRANCINE; DE LIMA, FRANCIELE; DE PAULA, ERICH VINICIUS. HRT Atlas v1.0 database: redefining human and mouse housekeeping genes and candidate reference transcripts by mining massive RNA-seq datasets. Nucleic Acids Research, v. 49, n. D1, p. D947-D955, JAN 8 2021. Web of Science Citations: 2.
GOMES SANTATERRA, VANESSA ARAUJO; LUZ FIUSA, MAIARA MARX; HOUNKPE, BIDOSSESSI WILFRIED; CHENOU, FRANCINE; TONASSE, WOUITCHEKPO VINCENT; GOMES DA COSTA, LOREDANA NILKENES; GARCIA-WEBER, DIEGO; DOMINGOS, IGOR DE FARIAS; DE LIMA, FRANCIELE; BORBA-JUNIOR, IVANIO TEIXEIRA; ARAUJO, ADERSON DA SILVA; LUCENA-ARAUJO, ANTONIO ROBERTO; CAVALCANTE BEZERRA, MARCOS ANDRE; NUNES DOS SANTOS, MAGNUN NUELDO; COSTA, FERNANDO FERREIRA; MILLAN, JAIME; DE PAULA, ERICH VINICIUS. Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients. FRONTIERS IN IMMUNOLOGY, v. 11, DEC 14 2020. Web of Science Citations: 0.
HOUNKPE, BIDOSSESSI WILFRIED; CHENOU, FRANCINE; DOMINGOS, IGOR DE FARIAS; CARDOSO, EVILAZIO CUNHA; COSTA SOBREIRA, MARCONDES JOSE DE VASCONCELOS; ARAUJO, ADERSON S.; LUCENA-ARAUJO, ANTONIO ROBERTO; DA SILVA NETO, PEDRO VIEIRA; MALHEIRO, ADRIANA; FRAIJI, NELSON ABRAHIM; COSTA, FERNANDO FERREIRA; BEZERRA, MARCOS ANDRE C.; SANTOS, MAGNUN NUELDO NUNES; DE PAULA, ERICH VINICIUS. Neutrophil extracellular trap regulators in sickle cell disease: Modulation of gene expression of PADI4, neutrophil elastase, and myeloperoxidase during vaso-occlusive crisis. RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, v. 5, n. 1 DEC 2020. Web of Science Citations: 0.
MARTINS, T. D.; ANNICHINO-BIZZACCHI, J. M.; ROMANO, A. V. C.; MACIEL FILHO, R. Artificial neural networks for prediction of recurrent venous thromboembolism. INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS, v. 141, SEP 2020. Web of Science Citations: 0.
MAZETTO, BRUNA DE MORAES; LAZARINI, MARIANA; TOBALDINI, LAIS QUINTEIRO; ARANTES, FERNANDA TALGE; DOS SANTOS, ANA PAULA ROSA; JACINTO, BRUNA CARDOSO; VAZ, CAMILA DE OLIVEIRA; MESQUITA, GABRIELA TRIPIQUIA VECHIATTO; SARAIVA, SABRINA DA SILVA; ANNICHINO-BIZZACCHI, JOYCE; ORSI, FERNANDA ANDRADE. Expression of tissue factor mRNA in thrombosis associated with antiphospholipid syndrome. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, v. 51, n. 2 JUL 2020. Web of Science Citations: 0.
ARANTES, FERNANDA T.; MAZETTO, BRUNA M.; SARAIVA, SABRINA S.; TOBALDINI, LAIS Q.; DOS SANTOS, ANA PAULA R.; ANNICHINO-BIZZACCHI, JOYCE; ORSI, FERNANDA A. Inflammatory markers in thrombosis associated with primary antiphospholipid syndrome. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, MAY 2020. Web of Science Citations: 0.
BITTAR, LUIS FERNANDO; DA SILVA, LETICIA QUEIROZ; DE ANDRADE ORSI, FERNANDA LOUREIRO; SENGER ZAPPONI, KIARA CRISTINA; MAZETTO, BRUNA DE MORAES; DE PAULA, ERICH VINICIUS; DE LIMA MONTALVAO, SILMARA APARECIDA; ANNICHINO-BIZZACCHI, JOYCE MARIA. Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome. PLoS One, v. 15, n. 1 JAN 16 2020. Web of Science Citations: 1.
FERREIRA, TATIANE; HUBER, STEPHANY CARES; MARTINELLI, BEATRIZ DE MORAES; LEMOS JUNIOR, ARLINDO; MENEZES, FABIO HUSEMANN; ORSI, FERNANDA ANDRADE; BITTAR, LUIS FERNANDO; GERBASE DE OLIVEIRA, LUIZ FREDERICO; SODRE, LEONARDO RAGAZZI; MELLO, TAYANA TEIXEIRA; RIELLI, GLAUBER; COLELLA, MARINA PEREIRA; DE PAULA, ERICH VINICIUS; YAMAGUTI-HAYAKAWA, GABRIELA G.; MONTALVAO, SILMARA; ANNICHINO-BIZZACCHI, JOYCE M. Low prevalence of Post-thrombotic syndrome in patients treated with rivaroxaban. VASCULAR PHARMACOLOGY, v. 124, JAN 2020. Web of Science Citations: 0.
CAMPOS NOGUEIRA, YZABELLA ALVES; GOMES DA COSTA, LOREDANA NILKENES; LEVY, CARLOS EMILIO; ORSI, FERNANDA ANDRADE; DE LIMA, FRANCIELE; ANNICHINNO-BIZZACCHI, JOYCE M.; DE PAULA, ERICH VINICIUS. Hypofibrinolysis induced by tranexamic acid does not influence inflammation and mortality in a polymicrobial sepsis model. PLoS One, v. 14, n. 12 DEC 31 2019. Web of Science Citations: 0.
MARTINS, TIAGO D.; ANNICHINO-BIZZACCHI, JOYCE M.; ROMANO, ANNA V. C.; MACIEL FILHO, RUBENS. Principal Component Analysis on Recurrent Venous Thromboembolism. CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS, v. 25, DEC 19 2019. Web of Science Citations: 0.
NOBREGA BARBOSA, AYLA CRISTINA; LIMA MONTALVAO, SILMARA APARECIDA; NOBREGA BARBOSA, KEVAN GUILHERME; COLELLA, MARINA PEREIRA; ANNICHINO-BIZZACCHI, JOYCE MARIA; OZELO, MARGARETH CASTRO; DE PAULA, ERICH VINICIUS. Prolonged APTT of unknown etiology: A systematic evaluation of causes and laboratory resource use in an outpatient hemostasis academic unit. RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, v. 3, n. 4, p. 749-757, OCT 2019. Web of Science Citations: 0.
TOBALDINI, LAIS QUINTEIRO; ARANTES, FERNANDA TALGE; SARAIVA, SABRINA DA SILVA; MAZETTO, BRUNA DE MORAES; COLELLA, MARINA PEREIRA; DE PAULA, ERICH VINICIUS; ANNICHINO-BIZZACHI, JOYCE; ORSI, FERNANDA ANDRADE. Circulating levels of tissue factor and the risk of thrombosis associated with antiphospholipid syndrome. THROMBOSIS RESEARCH, v. 171, p. 114-120, NOV 2018. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.