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148 results on '"Glembotsky, A. C."'

1. Association of laboratory test results with the bleeding history in patients with inherited platelet function disorders (the Bleeding Assesment Tool - LABoratory tests substudy): communication from the Platelet Physiology ISTH-SSC

Author

Gresele, Paolo, Falcinelli, Emanuela, Bury, Loredana, Alessi, Marie-Christine, Guglielmini, Giuseppe, Falaise, Céline, Podda, Gianmarco, Fiore, Mathieu, Mazziotta, Francesco, Sevivas, Teresa, Bermejo, Nuria, De Candia, Erica, Chitlur, Meera, Lambert, Michele P., Barcella, Luca, Glembotsky, Ana C., and Lordkipanidzé, Marie

Published
2024
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3. Two novel families with RUNX1 variants indicate glycine 168 as a new mutational hotspot: Implications for FPD/AML diagnosis.

Author

Kamiya, Laureano J., Barozzi, Serena, Isidori, Federica, Ganiewich, Daiana, De Luca, Geraldine, Bozzi, Valeria, Marta, Rosana F., Melazzini, Federica, Pippucci, Tommaso, Heller, Paula G., Glembotsky, Ana C., and Pecci, Alessandro

Subjects
GENETIC disorders, MISSENSE mutation, AMINO acids, STRUCTURAL models, LEUKEMIA
Abstract

Correct interpretation of the pathogenicity of germline RUNX1 variants is essential for FPD/AML diagnosis, clinical management and leukaemia surveillance. We report two families with clear FPD/AML phenotypic features harbouring missense variants at RHD critical residue Gly168. Although classified as of unknown significance (VUS) by RUNX1‐specific curation guidelines, these variants should rather be considered likely pathogenic, as supported by computational tools, structural modelling and dysregulated platelet expression of RUNX1‐targets, adding Gly168 among amino acids currently recognised as mutational hotspots. Our data could help reduce the number of variants classified as VUS, providing evidence for updating RUNX1 guidelines, thus improving FPD/AML diagnosis. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Elevated levels of damageassociated molecular patterns HMGB1 and S100A8/A9 coupled with toll-like receptor-triggered monocyte activation are associated with inflammation in patients with myelofibrosis.

Author

De Luca, Geraldine, Goette, Nora P., Lev, Paola R., Baroni Pietto, Maria C., Marin Oyarzún, Cecilia P., Castro Rıós, Miguel A., Moiraghi, Beatriz, Sackmann, Federico, Kamiya, Laureano J., Verri, Veronica, Caula, Victoria, Fernandez, Vanina, Vicente, Angeles, Pose Cabarcos, Julio, Caruso, Vanesa, Camacho, Maria F., Larripa, Irene B., Khoury, Marina, Marta, Rosana F., and Glembotsky, Ana C.

Subjects
INFLAMMATION, INFLAMMATORY mediators, CELL-free DNA, TOLL-like receptors, DISEASE progression, MYELOFIBROSIS
Abstract

Inflammation plays a pivotal role in the pathogenesis of primary and post-essential thrombocythemia or post-polycythemia vera myelofibrosis (MF) in close cooperation with the underlying molecular drivers. This inflammatory state is induced by a dynamic spectrum of inflammatory cytokines, although recent evidence points to the participation of additional soluble inflammatory mediators. Damage-associated molecular patterns (DAMPs) represent endogenous signals released upon cell death or damage which trigger a potent innate immune response. We assessed the contribution of two prototypical DAMPs, HMGB1 and S100A8/A9, to MF inflammation. Circulating HMGB1 and S100A8/A9 were elevated in MF patients in parallel to the degree of systemic inflammation and levels increased progressively during advanced disease stages. Patients with elevated DAMPs had higher frequency of adverse clinical features, such as anemia, and inferior survival, suggesting their contribution to disease progression. Monocytes, which are key players inMF inflammation, were identified as a source of S100A8/A9 but not HMGB1 release, while both DAMPs correlated with cell death parameters, such as serumLDH and cell-free DNA, indicating that passive release is an additional mechanism leading to increased DAMPs. HMGB1 and S100A8/A9 promote inflammation through binding to Toll-like receptor (TLR) 4, whereas the former also binds TLR2. Monocytes from MF patients were shown to be hyperactivated at baseline, as reflected by higher CD11b and tissue factor exposure and increased expression levels of proinflammatory cytokines IL-1b and IL-6. Patient monocytes showed preserved TLR4 and TLR2 expression and were able to mount normal or even exacerbated functional responses and cytokine upregulation following stimulation of TLR4 and TLR2. Elevated levels of endogenous TLR ligands HMGB1 and S100A8/A9 coupled to the finding of preserved or hyperreactive TLR-triggered responses indicate that DAMPs may promote monocyte activation and cytokine production in MF, fueling inflammation. Plasma IL-1b and IL-6 were elevated in MF and correlated with DAMPs levels, raising the possibility that DAMPs could contribute to cytokine generation in vivo. In conclusion, this study highlights that, in cooperation with classic proinflammatory cytokines, DAMPs represent additional inflammatory mediators that may participate in the generation of MF inflammatory state, potentially providing novel biomarkers of disease progression and new therapeutic targets. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Elevated levels of damage-associated molecular patterns HMGB1 and S100A8/A9 coupled with toll-like receptor-triggered monocyte activation are associated with inflammation in patients with myelofibrosis.

Author

De Luca, Geraldine, Goette, Nora P., Lev, Paola R., Baroni Pietto, Maria C., Marin Oyarzún, Cecilia P., Castro Ríos, Miguel A., Moiraghi, Beatriz, Sackmann, Federico, Kamiya, Laureano J., Verri, Veronica, Caula, Victoria, Fernandez, Vanina, Vicente, Angeles, Pose Cabarcos, Julio, Caruso, Vanesa, Camacho, Maria F., Larripa, Irene B., Khoury, Marina, Marta, Rosana F., and Glembotsky, Ana C.

Subjects
INFLAMMATION, INFLAMMATORY mediators, CELL-free DNA, TOLL-like receptors, DISEASE progression, MYELOFIBROSIS
Abstract

Inflammation plays a pivotal role in the pathogenesis of primary and post-essential thrombocythemia or post-polycythemia vera myelofibrosis (MF) in close cooperation with the underlying molecular drivers. This inflammatory state is induced by a dynamic spectrum of inflammatory cytokines, although recent evidence points to the participation of additional soluble inflammatory mediators. Damage-associated molecular patterns (DAMPs) represent endogenous signals released upon cell death or damage which trigger a potent innate immune response. We assessed the contribution of two prototypical DAMPs, HMGB1 and S100A8/A9, to MF inflammation. Circulating HMGB1 and S100A8/A9 were elevated in MF patients in parallel to the degree of systemic inflammation and levels increased progressively during advanced disease stages. Patients with elevated DAMPs had higher frequency of adverse clinical features, such as anemia, and inferior survival, suggesting their contribution to disease progression. Monocytes, which are key players inMF inflammation, were identified as a source of S100A8/A9 but not HMGB1 release, while both DAMPs correlated with cell death parameters, such as serumLDH and cell-free DNA, indicating that passive release is an additional mechanism leading to increased DAMPs. HMGB1 and S100A8/A9 promote inflammation through binding to Toll-like receptor (TLR) 4, whereas the former also binds TLR2. Monocytes from MF patients were shown to be hyperactivated at baseline, as reflected by higher CD11β and tissue factor exposure and increased expression levels of proinflammatory cytokines IL-1β and IL-6. Patient monocytes showed preserved TLR4 and TLR2 expression and were able to mount normal or even exacerbated functional responses and cytokine upregulation following stimulation of TLR4 and TLR2. Elevated levels of endogenous TLR ligands HMGB1 and S100A8/A9 coupled to the finding of preserved or hyperreactive TLR-triggered responses indicate that DAMPs may promote monocyte activation and cytokine production in MF, fueling inflammation. Plasma IL-1β and IL-6 were elevated in MF and correlated with DAMPs levels, raising the possibility that DAMPs could contribute to cytokine generation in vivo. In conclusion, this study highlights that, in cooperation with classic proinflammatory cytokines, DAMPs represent additional inflammatory mediators that may participate in the generation of MF inflammatory state, potentially providing novel biomarkers of disease progression and new therapeutic targets. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: A communication from the Platelet Physiology SSC

Author

Gresele, Paolo, Orsini, Sara, Noris, Patrizia, Falcinelli, Emanuela, Alessi, Marie Christine, Bury, Loredana, Borhany, Munira, Santoro, Cristina, Glembotsky, Ana C., Cid, Ana Rosa, Tosetto, Alberto, De Candia, Erica, Fontana, Pierre, Guglielmini, Giuseppe, Pecci, Alessandro, Heller, Paula G., Rodorigo, Giuseppina, Lammle, Bernhard, Trinchero, Alice, Paolo, Radossi, Ferrari, Silvia, Rancitelli, Davide, Stolinski, Amy, Arulselvan, Abinaya, Lassandro, Giuseppe, Luceros, Analia Sanchez, Jandrot‐Perrus, Martine, Kunishima, Shinji, Rivera Pozo, José, Lordkipanidzé, Marie, Melazzini, Federica, Falaise, Céline, Casonato, Alessandra, Podda, Gianmarco, Kannan, Meganathan, Jurk, Kerstin, Sevivas, Teresa, Castaman, Giancarlo, Grandone, Elvira, Fiore, Mathieu, Zuniga, Pamela, Henskens, Yvonne, Miyazaki, Koji, Dupuis, Arnaud, Hayward, Catherine, Zaninetti, Carlo, Abid, Madiha, Ferrara, Grazia, Mazzucconi, Maria Gabriella, Tagariello, Giuseppe, James, Paula, Fabris, Fabrizio, Russo, Alexandra, Bermejo, Nuria, Napolitano, Mariasanta, Curnow, Jennifer, Vasiliki, Gkalea, Zieger, Barbara, Fedor, Marian, Chitlur, Meera, Lambert, Michele, Barcella, Luca, Cosmi, Benilde, Giordano, Paola, Porri, Claudia, Eker, Ibrahim, Morel‐Kopp, Marie‐Christine, Deckmyn, Hans, Frelinger, Andrew L., III, Harrison, Paul, Mezzano, Diego, and Mumford, Andrew D.

Published
2020
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7. Association of laboratory test results with the bleeding history in patients with inherited platelet function disorders (the BAT-LAB substudy): communication from the Platelet Physiology ISTH-SSC

Author

Gresele, Paolo, primary, Falcinelli, Emanuela, additional, Bury, Loredana, additional, Alessi, Marie-Christine, additional, Guglielmini, Giuseppe, additional, Falaise, Céline, additional, Podda, Gianmarco, additional, Fiore, Mathieu, additional, Mazziotta, Francesco, additional, Sevivas, Teresa, additional, Bermejo, Nuria, additional, De Candia, Erica, additional, Chitlur, Meera, additional, Lambert, Michele P., additional, Barcella, Luca, additional, Glembotsky, Ana C., additional, and Lordkipanidzé, Marie, additional

Published
2023
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8. High cell-free DNA is associated with disease progression, inflammasome activation and elevated levels of inflammasome-related cytokine IL-18 in patients with myelofibrosis

Author

De Luca, Geraldine, primary, Lev, Paola R., additional, Camacho, Maria F., additional, Goette, Nora P., additional, Sackmann, Federico, additional, Castro Ríos, Miguel A., additional, Moiraghi, Beatriz, additional, Cortes Guerrieri, Veronica, additional, Bendek, Georgina, additional, Carricondo, Emiliano, additional, Enrico, Alicia, additional, Vallejo, Veronica, additional, Varela, Ana, additional, Khoury, Marina, additional, Gutierrez, Marina, additional, Larripa, Irene B., additional, Marta, Rosana F., additional, Glembotsky, Ana C., additional, and Heller, Paula G., additional

Published
2023
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14. A Deep Dive into the Pathology of Gray Platelet Syndrome: New Insights on Immune Dysregulation

Author

Glembotsky,Ana C, De Luca,Geraldine, and Heller,Paula G

Subjects
Journal of Blood Medicine
Abstract

Ana C Glembotsky,1,2 Geraldine De Luca,1,2 Paula G Heller1,2 1Departamento Hematología Investigación, Instituto de Investigaciones Médicas “Dr. A. Lanari”, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina; 2Departamento Hematología Investigación, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires, Instituto de Investigaciones Médicas (IDIM), Buenos Aires, ArgentinaCorrespondence: Paula G HellerDepartamento Hematología Investigación,Instituto de Investigaciones Médicas “Dr. A. Lanari”, Facultad de Medicina, Universidad de Buenos Aires, Combatientes de Malvinas 3150, Buenos Aires, 1427, ArgentinaTel +54 11 5287 3872Email paulaheller@hotmail.comAbstract: The gray platelet syndrome (GPS) is a rare platelet disorder, characterized by impaired alpha-granule biogenesis in megakaryocytes and platelets due to NBEAL2 mutations. Typical clinical features include macrothrombocytopenia, bleeding and elevated vitamin B12 levels, while bone marrow fibrosis and splenomegaly may develop during disease progression. Recently, the involvement of other blood lineages has been highlighted, revealing the role of NBEAL2 outside the megakaryocyte-platelet axis. Low leukocyte counts, decreased neutrophil granulation and impaired neutrophil extracellular trap formation represent prominent findings in GPS patients, reflecting deranged innate immunity and associated with an increased susceptibility to infection. In addition, low numbers and impaired degranulation of NK cells have been demonstrated in animal models. Autoimmune diseases involving different organs and a spectrum of autoantibodies are present in a substantial proportion of GPS patients, expanding the syndromic spectrum of this disorder and pointing to dysregulation of the adaptive immune response. Low-grade inflammation, as evidenced by elevation of liver-derived acute-phase reactants, is another previously unrecognized feature of GPS which may contribute to disease manifestations. This review will focus on the mechanisms underlying the pathogenesis of blood cell abnormalities in human GPS patients and NBEAL2-null animal models, providing insight into the effects of NBEAL2 in hemostasis, inflammation and immunity.Keywords: NBEAL2, gray platelet syndrome, α-granules, immune dysregulation, neutrophils

Published
2021

15. Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus

Author

Baroni Pietto, M. Constanza, primary, Lev, Paola R., additional, Glembotsky, Ana C., additional, Marín Oyarzún, Cecilia P., additional, Gomez, Graciela, additional, Collado, Victoria, additional, Pisoni, Cecilia, additional, Gomez, Ramiro A., additional, Grodzielski, Matías, additional, Gonzalez, Jacqueline, additional, Mariño, Karina V., additional, Heller, Paula G., additional, Goette, Nora P., additional, and Marta, Rosana F., additional

Published
2021
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16. Outcomes of 339 pregnancies in 181 women suffering from 13 different forms of inherited thrombocytopenia enrolled in a retrospective and multicentric study (on behalf of EHA-SWG on thrombocytopenias and platelet function disorders): WH09

Author

Noris, P, Schlegel, N, Klersy, C, Heller, P G, 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, M-F, Glembotsky, A C, Muñiz-Diaz, E, Randi, M L, Trillot, N, Bury, L, Lecompte, T, Marconi, C, Savoia, A, and Balduini, C L

Published
2014

19. The ISTH bleeding assessment tool as predictor of bleeding events in inherited platelet disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology

Author

Gresele, P., Falcinelli, E., Bury, L., Pecci, A., Alessi, M. -C., Borhany, M., Heller, P. G., Santoro, C., Cid, A. R., Orsini, S., Fontana, P., De Candia, E., Podda, G., Kannan, M., Jurk, K., Castaman, G., Falaise, C., Guglielmini, G., Noris, P., Zaninetti, C., Fiore, M., Tosetto, A., Zuniga, P., Miyazaki, K., Dupuis, A., Hayward, C., Casonato, A., Grandone, E., Mazzucconi, M. G., James, P., Fabris, F., Henskens, Y., Napolitano, M., Curnow, J., Gkalea, V., Fedor, M., Lambert, M. P., Zieger, B., Barcella, L., Cosmi, B., Giordano, P., Porri, C., Melazzini, F., Abid, M., Glembotsky, A. C., Ferrara, G., Russo, A., Deckmyn, H., Frelinger, A. L., Harrison, P., Mezzano, D., Mumford, A. D., Lordkipanidzé, M., BAT-VAL Study Investigators, Università degli Studi di Perugia = University of Perugia (UNIPG), 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), Unidad de Coagulopatías Congénitas. Hospital Universitario La Fe., Gresele, Paolo, Falcinelli, Emanuela, Bury, Loredana, Pecci, Alessandro, Alessi, Marie-Christine, Borhany, Munira, Heller, Paula G, Santoro, Cristina, Cid, Ana Rosa, Orsini, Sara, Fontana, Pierre, De Candia, Erica, Podda, Gianmarco, Kannan, Meganathan, Jurk, Kerstin, Castaman, Giancarlo, Falaise, Céline, Guglielmini, Giuseppe, Noris, Patrizia, Mariasanta Napolitano, Università degli Studi di Perugia (UNIPG), University of Perugia, Gresele, P., Falcinelli, E., Bury, L., Pecci, A., Alessi, M.-C., Borhany, M., Heller, P.G., Santoro, C., Cid, A.R., Orsini, S., Fontana, P., De Candia, E., Podda, G., Kannan, M., Jurk, K., Castaman, G., Falaise, C., Guglielmini, G., Noris, P., Zaninetti, C., Fiore, M., Tosetto, A., Zuniga, P., Miyazaki, K., Dupuis, A., Hayward, C., Casonato, A., Grandone, E., Mazzucconi, M.G., James, P., Fabris, F., Henskens, Y., Napolitano, M., Curnow, J., Gkalea, V., Fedor, M., Lambert, M.P., Zieger, B., Barcella, L., Cosmi, B., Giordano, P., Porri, C., Melazzini, F., Abid, M., Glembotsky, A.C., Ferrara, G., Russo, A., Deckmyn, H., Frelinger, A.L., Harrison, P., Mezzano, D., Mumford, A.D., Lordkipanidzé, M., and BAT-VAL Study Investigators

Subjects
medicine.medical_specialty, animal structures, mild&#8208, Platelet Function Tests, Platelet disorder, inherited platelet disorder, Hemorrhage, 030204 cardiovascular system & hematology, Hemorrhage/diagnosis, 03 medical and health sciences, 0302 clinical medicine, Von Willebrand factor, hemic and lymphatic diseases, Internal medicine, von Willebrand Factor, Von Willebrand disease, Medicine, Humans, Platelet, Bleeding prediction, Bleeding score, Blood platelet disorders, Child, Communication, Hemorrhage, Humans, Inherited platelet disorders, Mild-moderate bleeding disorders, Platelet Function Tests, von Willebrand diseases, von Willebrand Factor, Child, Blood Platelet Disorders, ddc:616, mild-moderate bleeding disorders, biology, business.industry, mild-moderate bleeding disorder, Incidence (epidemiology), Communication, Settore MED/09 - MEDICINA INTERNA, bleeding prediction, von Willebrand Diseases/diagnosis/genetics, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Blood Platelet Disorders/diagnosis/genetics, 3. Good health, bleeding score, Institutional repository, von Willebrand Diseases, moderate bleeding disorders, inherited platelet disorders, Quartile, biology.protein, von Willebrand disease, business
Abstract

Background: The ISTH Bleeding Assessment Tool (ISTH-BAT) has been validated for clinical screening of suspected von Willebrand disease (VWD) and for bleeding prediction. Recently it has been validated for subjects with inherited platelet disorders (IPD) (BAT-VAL study). Objectives: To determine whether the ISTH-BAT bleeding score (BS) predicts subsequent bleeding events requiring treatment in IPD patients. Methods: Patients with IPD, type 1 VWD (VWD-1) and age- and sex-matched healthy controls enrolled in the BAT-VAL study were prospectively followed-up for 2years and bleeding episodes requiring treatment were recorded. Results: Of the 1098 subjects initially enrolled, 955 were followed-up and 124 suffered hemorrhages during follow-up, 60% of whom had inherited platelet function disorders (IPFD). Total number of events was significantly higher in IPFD (n=235) than VWD-1 (n=52) or inherited thrombocytopenia (IT; n=20). Events requiring transfusions were 66% in IPFD, 5.7% in VWD-1, and 3% in IT. Baseline BS was significantly higher in IPFD patients with a bleeding event at follow-up than in those without (p&nbsp

Published
2021
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20. MYH9-Related Disease: A Novel Prognostic Model to Predict the Clinical Evolution of the Disease Based on Genotype–Phenotype Correlations

Author

Pecci, Alessandro, Klersy, Catherine, Gresele, Paolo, Lee, Kieran J.D., De Rocco, Daniela, Bozzi, Valeria, Russo, Giovanna, Heller, Paula G., Loffredo, Giuseppe, Ballmaier, Matthias, Fabris, Fabrizio, Beggiato, Eloise, Kahr, Walter H.A., Pujol-Moix, Nuria, Platokouki, Helen, Van Geet, Christel, Noris, Patrizia, Yerram, Preethi, Hermans, Cedric, Gerber, Bernhard, Economou, Marina, De Groot, Marco, Zieger, Barbara, De Candia, Erica, Fraticelli, Vincenzo, Kersseboom, Rogier, Piccoli, Giorgina B., Zimmermann, Stefanie, Fierro, Tiziana, Glembotsky, Ana C., Vianello, Fabrizio, Zaninetti, Carlo, Nicchia, Elena, Güthner, Christiane, Baronci, Carlo, Seri, Marco, Knight, Peter J., Balduini, Carlo L., and Savoia, Anna

Published
2014
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21. Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus.

Author

Baroni Pietto, M. Constanza, Lev, Paola R., Glembotsky, Ana C., Marín Oyarzún, Cecilia P., Gomez, Graciela, Collado, Victoria, Pisoni, Cecilia, Gomez, Ramiro A., Grodzielski, Matías, Gonzalez, Jacqueline, Mariño, Karina V., Heller, Paula G., Goette, Nora P., and Marta, Rosana F.

Subjects
THROMBOPOIETIN receptors, CORD blood, PLATELET count, THROMBOCYTOPENIA, BLOOD platelet disorders, MEMBRANE potential, MITOCHONDRIAL membranes, SYSTEMIC lupus erythematosus
Abstract

Systemic lupus erythematosus (SLE) is an autoimmune condition developing thrombocytopenia in about 10–15% of cases, however, mechanisms leading to low platelet count were not deeply investigated in this illness. Here we studied possible causes of thrombocytopenia, including different mechanisms of platelet clearance and impairment in platelet production. Twenty-five SLE patients with and without thrombocytopenia were included. Platelet apoptosis, assessed by measurement of loss of mitochondrial membrane potential, active caspase 3 and phosphatidylserine exposure, was found to increase in thrombocytopenic patients. Plasma from 67% SLE patients (thrombocytopenic and non-thrombocytopenic) induced loss of sialic acid (Ricinus communis agglutinin I and/or Peanut agglutinin binding) from normal platelet glycoproteins. Concerning platelet production, SLE plasma increased megakaryopoiesis (evaluated using normal human cord blood CD34+ hematopoietic progenitors), but inhibited thrombopoiesis (proplatelet count). Anti-platelet autoantibody depletion from SLE plasma reverted this inhibition. Overall, abnormalities were more frequently observed in thrombocytopenic than non-thrombocytopenic SLE patients and in those with active disease (SLEDAI≥5). In conclusion, platelet clearance due to apoptosis and desialylation, and impaired platelet production mainly due to inhibition of thrombopoiesis, could be relevant mechanisms leading to thrombocytopenia in SLE. These findings could provide a rational basis for the choice of proper therapies to correct platelet counts in these patients. [ABSTRACT FROM AUTHOR]

Published
2022
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23. Platelet Toll-Like Receptors Mediate Thromboinflammatory Responses in Patients With Essential Thrombocythemia

Author

Marín Oyarzún, Cecilia P., primary, Glembotsky, Ana C., additional, Goette, Nora P., additional, Lev, Paola R., additional, De Luca, Geraldine, additional, Baroni Pietto, María C., additional, Moiraghi, Beatriz, additional, Castro Ríos, Miguel A., additional, Vicente, Angeles, additional, Marta, Rosana F., additional, Schattner, Mirta, additional, and Heller, Paula G., additional

Published
2020
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28. Gray platelet syndrome: Novel mutations of the NBEAL2 gene

Author

Bottega Roberta, Nicchia Elena, Alfano Caterina, Glembotsky Ana C., Pastore Annalisa, Bertaggia-Calderara Debora, Bisig Bettina, Duchosal Michel A., Arbesú Guillermo, Alberio Lorenzo, Heller Paula G., Savoia Anna, Bottega, Roberta, Nicchia, Elena, Alfano, Caterina, Glembotsky, Ana C., Pastore, Annalisa, Bertaggia Calderara, Debora, Bisig, Bettina, Duchosal, Michel A., Arbesú, Guillermo, Alberio, Lorenzo, Heller, Paula G., Savoia, Anna, Glembotsky Ana, C., Bertaggia-Calderara, Debora, Duchosal Michel, A., and Heller Paula, G.

Subjects
Salud Ocupacional, CIENCIAS MÉDICAS Y DE LA SALUD, gray platelet syndrome, platelets, Ciencias de la Salud, Hematology, NBEAL2, mutations
Abstract

Gray platelet syndrome (GPS) is a rare inherited macrothrombocytopenia characterized by reduction of a-granules in platelets and megakaryocytes associated with mild-tomoderate bleeding and myelofibrosis [1]. As reported in at least 28 unrelated families [1], GPS is caused by mutations of NBEAL2, the gene encoding for the neurobeachin-like-2 protein. NBEAL2 is a member of the family containing the BEACH (BEige And Chediak Higashi) domain, a conserved region involved in vesicular trafficking that may be critical for the a-granule development [2]. Here, we report novel mutations of NBEAL2 in two affected individuals (P1 and P2), who were previously diagnosed with immune thrombocytopenia (ITP) and then suspected to have GPS because of absence of azurophilic granules on May-Grunwald-Giemsa staining. In P1, sequencing analysis identified an € homozygous missense variant (c.6212G > C; p.Arg2071Pro; Supporting Information Fig. S1). Since her parents were not available for the segregation analysis, we hypothesised that the two mutant alleles were identical by descent because of homozygosity of all the polymorphic markers at the NBEAL2 locus (data not shown). Moreover, the potential hemizygous condition was excluded using statistical analyses of NBEAL2 amplicon coverage as previously reported (Supporting Information Fig. S1C) [3]. In P2, we detected one maternal nonsense (c.3839C > T; p.Arg1280*) and one paternal missense (c.6477C > G; p.His2159Gln; Supporting Information Fig. S1). The three NBEAL2 variants are reported in SNPs databases but with a minor allele frequency

Published
2017
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29. Publisher Correction: Multiple concomitant mechanisms contribute to low platelet count in patients with immune thrombocytopenia

Author

Grodzielski, Matías, primary, Goette, Nora P., additional, Glembotsky, Ana C., additional, Constanza Baroni Pietto, M., additional, Méndez-Huergo, Santiago P., additional, Pierdominici, Marta S., additional, Montero, Verónica S., additional, Rabinovich, Gabriel A., additional, Molinas, Felisa C., additional, Heller, Paula G., additional, Lev, Paola R., additional, and Marta, Rosana F., additional

Published
2020
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30. Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study

Author

Paciullo, Francesco, primary, Bury, Loredana, additional, Noris, Patrizia, additional, Falcinelli, Emanuela, additional, Melazzini, Federica, additional, Orsini, Sara, additional, Zaninetti, Carlo, additional, Abdul-Kadir, Rezan, additional, Obeng-Tuudah, Deborah, additional, Heller, Paula G., additional, Glembotsky, Ana C., additional, Fabris, Fabrizio, additional, Rivera, Jose, additional, Lozano, Maria Luisa, additional, Butta, Nora, additional, Favier, Remi, additional, Cid, Ana Rosa, additional, Fouassier, Marc, additional, Podda, Gian Marco, additional, Santoro, Cristina, additional, Grandone, Elvira, additional, Henskens, Yvonne, additional, Nurden, Paquita, additional, Zieger, Barbara, additional, Cuker, Adam, additional, Devreese, Katrien, additional, Tosetto, Alberto, additional, De Candia, Erica, additional, Dupuis, Arnaud, additional, Miyazaki, Koji, additional, Othman, Maha, additional, and Gresele, Paolo, additional

Published
2019
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31. Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study

Author

Paciullo, Francesco, Bury, Loredana, Noris, Patrizia, Falcinelli, Emanuela, Melazzini, Federica, Orsini, Sara, Zaninetti, Carlo, Abdul-Kadir, Rezan, Obeng-Tuudah, Deborah, Heller, Paula, Glembotsky, Ana C, Fabris, Fabrizio, Rivera, Jose, Lozano, Maria Luisa, Butta, Nora, Favier, Remi, Cid, Ana Rosa, Fouassier, Marc, Podda, Gian Marco, Santoro, Cristina, Grandone, Elvira, Henskens, Yvonne, Nurden, Paquita, Zieger, Barbara, Cuker, Adam, Devreese, Katrien, Tosetto, Alberto, De Candia, Erica, Dupuis, Arnaud, Miyazaki, Koji, Othman, Maha, Gresele, Paolo, De Candia, Erica (ORCID:0000-0003-0942-2819), Paciullo, Francesco, Bury, Loredana, Noris, Patrizia, Falcinelli, Emanuela, Melazzini, Federica, Orsini, Sara, Zaninetti, Carlo, Abdul-Kadir, Rezan, Obeng-Tuudah, Deborah, Heller, Paula, Glembotsky, Ana C, Fabris, Fabrizio, Rivera, Jose, Lozano, Maria Luisa, Butta, Nora, Favier, Remi, Cid, Ana Rosa, Fouassier, Marc, Podda, Gian Marco, Santoro, Cristina, Grandone, Elvira, Henskens, Yvonne, Nurden, Paquita, Zieger, Barbara, Cuker, Adam, Devreese, Katrien, Tosetto, Alberto, De Candia, Erica, Dupuis, Arnaud, Miyazaki, Koji, Othman, Maha, Gresele, Paolo, and De Candia, Erica (ORCID:0000-0003-0942-2819)

Abstract

Major surgery is associated with an increased risk of venous thromboembolism, thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of venous thromboembolism in patients with inherited platelet disorders undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in inherited platelet disorders patients undergoing surgery at venous thromboembolism-risk participating in the multicenter SPATA study. We evaluated 210 surgical procedures carried out in 155 patients with well-defined forms of inherited platelet disorders (venous thromboembolism-risk: 31% high, 28.6% intermediate, 25.2% low, 15.2% very low). The use of thromboprophylaxis was low (23.3% of procedures), with higher prevalence in orthopedic and gynecological surgeries, and was related to venous thromboembolism-risk. The most frequently employed thromboprophylaxis was mechanical and appeared to be effective, as no patients developed thrombosis, including patients belonging to the highest venous thromboembolism-risk classes. Low-molecular-weight-heparin use was low (10.5%) and it did not influence the incidence of post-surgical bleeding or of antihemorrhagic prohemostatic interventions. Two thromboembolic events were registered, both occurring after high venous thromboembolism-risk procedures in patients who did not receive thromboprophylaxis (4.7%). Our findings suggest that venous thromboembolism incidence is low in patients with inherited platelet disorders undergoing surgery at venous thromboembolism-risk and that it is predicted by the Caprini score. Mechanical thromboprophylaxis may be of benefit in patients with inherited platelet disorders undergoing invasive procedures at venous thromboembolism-risk and low-molecular-weight-heparin should be considered for ma

Published
2019

32. Multiple concomitant mechanisms contribute to low platelet count in patients with immune thrombocytopenia

Author

Grodzielski, Matías, primary, Goette, Nora P., additional, Glembotsky, Ana C., additional, Constanza Baroni Pietto, M., additional, Méndez-Huergo, Santiago P., additional, Pierdominici, Marta S., additional, Montero, Verónica S., additional, Rabinovich, Gabriel A., additional, Molinas, Felisa C., additional, Heller, Paula G., additional, Lev, Paola R., additional, and Marta, Rosana F., additional

Published
2019
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33. Downregulation of TREM-like transcript-1 and collagen receptor α2 subunit, two novel RUNX1-targets, contributes to platelet dysfunction in familial platelet disorder with predisposition to acute myelogenous leukemia

Author

Glembotsky, Ana C., primary, Sliwa, Dominika, additional, Bluteau, Dominique, additional, Balayn, Nathalie, additional, Marin Oyarzún, Cecilia P., additional, Raimbault, Anna, additional, Bordas, Marie, additional, Droin, Nathalie, additional, Pirozhkova, Iryna, additional, Washington, Valance, additional, Goette, Nora P., additional, Marta, Rosana F., additional, Favier, Rémi, additional, Raslova, Hana, additional, and Heller, Paula G., additional

Published
2018
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34. Bleeding risk of surgery and its prevention in patients with inherited platelet disorders. The Surgery in Platelet disorders And Therapeutic Approach (SPATA) study

Author

Orsini, Sara, Noris, Patrizia, Bury, Loredana, Heller, Paula G, Santoro, Cristina, Kadir, Rezan A, Butta, Nora C, Falcinelli, Emanuela, Cid, Ana Rosa, Fabris, Fabrizio, Fouassier, Marc, Miyazaki, Koji, Lozano, Maria Luisa, Zuñiga, Pamela, Flaujac, Claire, Podda, GIAN MARCO, Bermejo, Nuria, Favier, Remi, Henskens, Yvonne, De Maistre, Emmanuel, DE CANDIA, Erica, Mumford, Andrew D, Ozdemir, Nihal G, Eker, Ibrahim, Nurden, Paquita, Bayart, Sophie, Lambert, Michele P, Bussel, James, Zieger, Barbara, Tosetto, Alberto, Melazzini, Federica, Glembotsky, Ana C, Pecci, Alessandro, Cattaneo, MARCO NATALE, Schlegel, Nicole, and Gresele, Paolo

Subjects
INHERITED THROMBOCYTOPENIA, Platelets, CIENCIAS MÉDICAS Y DE LA SALUD, SURGERY, Disorders of Platelet Function, Settore MED/09 - MEDICINA INTERNA, Medicina Clínica, bacterial infections and mycoses, PLATELETS, bleeding risk, inherited platelet disorders, BLEEDING, purl.org/becyt/ford/3.2 [https], Journal Article, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, purl.org/becyt/ford/3 [https], Medicina Critica y de Emergencia, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders (IPD), however very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a multicentric, retrospective worldwide study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted and their efficacy in patients with IPDs by rating the outcome of 829 surgical procedures carried out in 423 patients with well defined forms of IPD (238 inherited platelet function disorders -IPFD- and 185 inherited platelet number disorders-IPND-). Frequency of surgical bleeding was high in patients with IPD (19.7%), with a significantly higher bleeding incidence in IPFDs (24.8%) than in IPNDs (13.4%). The frequency of bleeding varied according to the type of IPD, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%), and was predicted by a preoperative WHO bleeding score >/-2. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urologic surgery. The use of preoperative prohemostatic treatments was associated with a lower bleeding frequency in patients with IPFD but not in IPNDs. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in IPD is substantial, especially in IPFDs, and bleeding history, type of disorder, type of surgery and female gender are associated with higher bleeding frequency. Prophylactic preoperative prohemostatic treatments appear to be required and associated with a lower bleeding incidence. Fil: Orsini, Sara. Università di Perugia; Italia Fil: Noris, Patrizia. University Of Pavia. Policlinico San Matteo; Italia Fil: Bury, Loredana. Università di Perugia; Italia Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Santoro, Cristina. Università degli studi di Roma ; Italia Fil: Kadir RA. Royal Free Hospital; Reino Unido Fil: Butta, Nora C.. Hospital Universitario la Paz; España Fil: Falcinelli, Emanuela. Università di Perugia; Italia Fil: Cid, Ana Rosa. Hospital Universitario y Politecnico ; España Fil: Fabris, Fabrizio. Università di Padova; Italia Fil: Fouassier, Marc. Centre Hospitalier Universitaire de Nantes; Francia Fil: Miyazaki, Koji. Kitasato University. School Of Medicine; Japón Fil: Lozano, Maria Luisa. Universidad Carlos III de Madrid. Instituto de Salud; España Fil: Zuñiga, Pamela. Pontificia Universidad Católica de Chile; Chile Fil: Flaujac, Claire. Cochin Hospital; Francia Fil: Podda, Gian Marco. Università degli Studi di Milano; Italia Fil: Bermejo, Nuria. Hospital ; España Fil: Favier, Remi. French Reference Centre For Inherited Platelet Disorder; Francia Fil: Henskens, Yvonne. Maastricht University. Medical Centre; Países Bajos Fil: De Maistre, Emmanuel. Centre Hospitalier Universitaire Dijon; Francia Fil: De Candia, Erica. Universitá Cattolica Sacro. Policlinico Agostino Gemelli; Italia Fil: Mumford, Andrew. University Of Bristol. School Of Clinical Sciences; Reino Unido Fil: Ozdemir, Gul Nihal. Cerrahpasa Medical Faculty. Pediatric Hematology Depart; Turquía Fil: Eker, Ibrahim. Gülhane Military Medical Faculty. Pediatric Hematology; Turquía Fil: Nurden, Paquita. Xavier Arnozan Hospital; Francia Fil: Bayart, Sophie. Centre Régional de Traitement Des Hémophiles; Francia Fil: Lambert, Michele P. University of Pennsylvania; Estados Unidos Fil: Bussel, James. Weill Cornell Medicine; Estados Unidos Fil: Zieger, Barbara. University Medical Center Freiburg; Alemania Fil: Tosseto, Alberto. San Bortolo Hospital; Italia Fil: Melazzini, Federica. Università degli studi di Pavia. Policlinico San Matteo; Italia Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pecci, Alessandro. Università degli studi di Pavia. Policlinico San Matteo; Italia Fil: Cattaneo, Marco. Università degli Studi di Milano; Italia Fil: Schlegel, Nicole. Centre Hospitalier Universitaire ; Francia Fil: Gresele, Paolo. Università di Perugia; Italia

Published
2017
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35. Bleeding risk of surgery and its prevention in patients with inherited platelet disorders

Author

Orsini, Sara, primary, Noris, Patrizia, additional, Bury, Loredana, additional, Heller, Paula G., additional, Santoro, Cristina, additional, Kadir, Rezan A., additional, Butta, Nora C., additional, Falcinelli, Emanuela, additional, Cid, Ana Rosa, additional, Fabris, Fabrizio, additional, Fouassier, Marc, additional, Miyazaki, Koji, additional, Lozano, Maria Luisa, additional, Zúñiga, Pamela, additional, Flaujac, Claire, additional, Podda, Gian Marco, additional, Bermejo, Nuria, additional, Favier, Remi, additional, Henskens, Yvonne, additional, De Maistre, Emmanuel, additional, De Candia, Erica, additional, Mumford, Andrew D., additional, Ozdemir, Gul Nihal, additional, Eker, Ibrahim, additional, Nurden, Paquita, additional, Bayart, Sophie, additional, Lambert, Michele P., additional, Bussel, James, additional, Zieger, Barbara, additional, Tosetto, Alberto, additional, Melazzini, Federica, additional, Glembotsky, Ana C., additional, Pecci, Alessandro, additional, Cattaneo, Marco, additional, Schlegel, Nicole, additional, and Gresele, Paolo, additional

Published
2017
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36. Mutations ofRUNX1in families with inherited thrombocytopenia

Author

De Rocco, Daniela, primary, Melazzini, Federica, additional, Marconi, Caterina, additional, Pecci, Alessandro, additional, Bottega, Roberta, additional, Gnan, Chiara, additional, Palombo, Flavia, additional, Giordano, Paola, additional, Coccioli, Maria Susanna, additional, Glembotsky, Ana C., additional, Heller, Paula G., additional, Seri, Marco, additional, Savoia, Anna, additional, and Noris, Patrizia, additional

Published
2017
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39. Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-Antibodies

Author

Goette, Nora P., primary, Glembotsky, Ana C., additional, Lev, Paola R., additional, Grodzielski, Matías, additional, Contrufo, Geraldine, additional, Pierdominici, Marta S., additional, Espasandin, Yesica R., additional, Riveros, Dardo, additional, García, Alejandro J., additional, Molinas, Felisa C., additional, Heller, Paula G., additional, and Marta, Rosana F., additional

Published
2016
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40. Correction: Corrigendum: Abnormal proplatelet formation and emperipolesis in cultured human megakaryocytes from gray platelet syndrome patients

Author

Di Buduo, Christian A., primary, Alberelli, Maria Adele, additional, Glembotsky, Ana C., additional, Podda, Gianmarco, additional, Lev, Paola R., additional, Cattaneo, Marco, additional, Landolfi, Raffaele, additional, Heller, Paula G., additional, Balduini, Alessandra, additional, and De Candia, Erica, additional

Published
2016
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43. Long-term follow-up of essential thrombocythemia patients treated with anagrelide: subgroup analysis according toJAK2/CALR/MPLmutational status

Author

Mela Osorio, María J., primary, Ferrari, Luciana, additional, Goette, Nora P., additional, Gutierrez, Marina I., additional, Glembotsky, Ana C., additional, Maldonado, Ana C., additional, Lev, Paola R., additional, Alvarez, Clarisa, additional, Korin, Laura, additional, Marta, Rosana F., additional, Molinas, Felisa C., additional, and Heller, Paula G., additional

Published
2015
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44. Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome

Author

Larocca, Luigi M., primary, Heller, Paula G., additional, Podda, Gianmarco, additional, Pujol-Moix, Nuria, additional, Glembotsky, Ana C., additional, Pecci, Alessandro, additional, Alberelli, Maria Adele, additional, Balduini, Carlo L., additional, Landolfi, Raffaele, additional, Cattaneo, Marco, additional, and De Candia, Erica, additional

Published
2015
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45. Differential expression of SDF-1 receptor CXCR4 in molecularly defined forms of inherited thrombocytopenias.

Author

Salim, Juan P., Glembotsky, Ana C., Lev, Paola R., Marin Oyarzún, Cecilia P., Goette, Nora P., Molinas, Felisa C., Marta, Rosana F., and Heller, Paula G.

Subjects
*THROMBOCYTOPENIA, *BLOOD platelet aggregation, *MEGAKARYOCYTES, *GENE expression, *RNA
Abstract

The SDF-1-CXCR4 axis plays an essential role in the regulation of platelet production, by directing megakaryocyte (MK) migration toward the vascular niche, thus allowing terminal maturation and proplatelet formation, and also regulates platelet function in an autocrine manner. Inherited thrombocytopenias (IT) comprise a spectrum of diverse clinical conditions caused by mutations in genes involved in platelet production and function. We assessed CXCR4 expression and SDF-1 levels in a panel of well-characterized forms of IT. Decreased surface CXCR4 levels were found in 8 of 27 (29.6%) IT patients by flow cytometry, including 4 of 6 patients with ANKRD26-RT, 3 of 3 patients with GPS and 1 of 6 patients with FPD/AML. Low CXCR4 levels were associated with impaired SDF-1-triggered platelet aggregation, indicating that this decrease is functionally relevant, whereas a normal platelet response was shown in patients harbouring preserved membrane CXCR4. Reduced CXCR4 was not due to decreased gene expression, as platelet RNA levels were normal or increased, suggesting a post-transcriptional defect. Increased ligand-induced receptor internalization was ruled out, as circulating SDF-1 levels were similar to controls. MK CXCR4 expression was normal, indicating that the defect in CXCR4 arises after the step of platelet biogenesis. In conclusion, the finding of defective CXCR4 expression specifically associated with certain IT disorders highlights the fact that abnormalities in several megakaryocytic regulators underlie IT pathogenesis and further reveal the heterogeneous nature of these conditions. [ABSTRACT FROM AUTHOR]

Published
2017
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46. MYH9-related disease: A novel prognostic model to predict the clinical evolution of the disease based on genotype-phenotype correlations

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de malformations vasculaires congénitales, Pecci, Alessandro, Klersy, Catherine, Gresele, Paolo, Lee, Kieran J.D., De Rocco, Daniela, Bozzi, Valeria, Russo, Giovanna, Heller, Paula G., Loffredo, Giuseppe, Ballmaier, Matthias, Fabris, Fabrizio, Beggiato, Eloise, Kahr, Walter H.A., Pujol-Moix, Nuria, Platokouki, Helen, Van Geet, Christel, Noris, Patrizia, Yerram, Preethi, Hermans, Cédric, Gerber, Bernhard, Economou, Marina, De Groot, Marco, Zieger, Barbara, De Candia, Erica, Fraticelli, Vincenzo, Kersseboom, Rogier, Piccoli, Giorgina B., Zimmermann, Stefanie, Fierro, Tiziana, Glembotsky, Ana C., Vianello, Fabrizio, Zaninetti, Carlo, Nicchia, Elena, Güthner, Christiane, Baronci, Carlo, Seri, Marco, Knight, Peter J., Balduini, Carlo L., Savoia, Anna, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de malformations vasculaires congénitales, Pecci, Alessandro, Klersy, Catherine, Gresele, Paolo, Lee, Kieran J.D., De Rocco, Daniela, Bozzi, Valeria, Russo, Giovanna, Heller, Paula G., Loffredo, Giuseppe, Ballmaier, Matthias, Fabris, Fabrizio, Beggiato, Eloise, Kahr, Walter H.A., Pujol-Moix, Nuria, Platokouki, Helen, Van Geet, Christel, Noris, Patrizia, Yerram, Preethi, Hermans, Cédric, Gerber, Bernhard, Economou, Marina, De Groot, Marco, Zieger, Barbara, De Candia, Erica, Fraticelli, Vincenzo, Kersseboom, Rogier, Piccoli, Giorgina B., Zimmermann, Stefanie, Fierro, Tiziana, Glembotsky, Ana C., Vianello, Fabrizio, Zaninetti, Carlo, Nicchia, Elena, Güthner, Christiane, Baronci, Carlo, Seri, Marco, Knight, Peter J., Balduini, Carlo L., and Savoia, Anna

Abstract

MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in the gene for nonmuscle myosin heavy chain IIA (NMMHC-IIA). MYH9-RD is characterized by a considerable variability in clinical evolution: patients present at birth with only thrombocytopenia, but some of them subsequently develop sensorineural deafness, cataract, and/or nephropathy often leading to end-stage renal disease (ESRD). We searched for genotype-phenotype correlations in the largest series of consecutive MYH9-RD patients collected so far (255 cases from 121 families). Association of genotypes with noncongenital features was assessed by a generalized linear regression model. The analysis defined disease evolution associated to seven different MYH9 genotypes that are responsible for 85% of MYH9-RD cases. Mutations hitting residue R702 demonstrated a complete penetrance for early-onset ESRD and deafness. The p.D1424H substitution associated with high risk of developing all the noncongenital manifestations of disease. Mutations hitting a distinct hydrophobic seam in the NMMHC-IIA head domain or substitutions at R1165 associated with high risk of deafness but low risk of nephropathy or cataract. Patients with p.E1841K, p.D1424N, and C-terminal deletions had low risk of noncongenital defects. These findings are essential to patients' clinical management and genetic counseling and are discussed in view of molecular pathogenesis of MYH9-RD. © 2013 WILEY PERIODICALS, INC.

Published
2014

47. Platelet Apoptosis in Adult Immune Thrombocytopenia. Relationship with Auto-Antibodies, Platelet Function and Treatment

Author

Contrufo, Geraldine, primary, Glembotsky, Ana C, additional, Goette, Nora P, additional, Lev, Paola R, additional, Grodzielski, Matías, additional, Pierdominici, Marta S, additional, Riveros, Dardo Alberto, additional, Montero, Verónica S, additional, García, Alejandro, additional, Molinas, Felisa C., additional, Heller, Paula G., additional, and Marta, Rosana F, additional

Published
2014
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48. MYH9-Related Disease: A Novel Prognostic Model to Predict the Clinical Evolution of the Disease Based on Genotype-Phenotype Correlations

Author

Pecci, Alessandro, primary, Klersy, Catherine, additional, Gresele, Paolo, additional, Lee, Kieran J.D., additional, De Rocco, Daniela, additional, Bozzi, Valeria, additional, Russo, Giovanna, additional, Heller, Paula G., additional, Loffredo, Giuseppe, additional, Ballmaier, Matthias, additional, Fabris, Fabrizio, additional, Beggiato, Eloise, additional, Kahr, Walter H.A., additional, Pujol-Moix, Nuria, additional, Platokouki, Helen, additional, Van Geet, Christel, additional, Noris, Patrizia, additional, Yerram, Preethi, additional, Hermans, Cedric, additional, Gerber, Bernhard, additional, Economou, Marina, additional, De Groot, Marco, additional, Zieger, Barbara, additional, De Candia, Erica, additional, Fraticelli, Vincenzo, additional, Kersseboom, Rogier, additional, Piccoli, Giorgina B., additional, Zimmermann, Stefanie, additional, Fierro, Tiziana, additional, Glembotsky, Ana C., additional, Vianello, Fabrizio, additional, Zaninetti, Carlo, additional, Nicchia, Elena, additional, Güthner, Christiane, additional, Baronci, Carlo, additional, Seri, Marco, additional, Knight, Peter J., additional, Balduini, Carlo L., additional, and Savoia, Anna, additional

Published
2013
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50. Application of a Diagnostic Algorithm for Inherited Thrombocytopenia Patients in the Setting of a Developing Country

Author

Glembotsky, Ana C, primary, Marta, Rosana F, additional, Espasandin, Yesica R, additional, Goette, Nora P, additional, Negro, Fernando, additional, Patrizia, Noris, additional, Savoia, Anna, additional, Pecci, Alessandro, additional, Balduini, Carlo Luigi, additional, Molinas, Felisa C., additional, and Heller, Paula G, additional

Published
2011
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