Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome

Autores
Larroca, Luigi M.; Heller, Paula Graciela; Podda, Gianmarco; Pujol Moix, Nuria; Glembotsky, Ana Claudia; Pecci, Alessandro; Alberelli, Maria Adele; Balduini, Carlo L.; Landolfi, Raffaele; Cattaneo, Marco; De Candia, Erica
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The gray platelet syndrome (GPS) is a rare congenital platelet disorder characterized by mild to moderate bleeding diathesis, macrothrombocytopenia and lack of azurophilic α-granules in platelets. Some platelet and megakaryocyte (MK) abnormalities have been described, but confirmative studies of the defects in larger patient cohorts have not been undertaken. We studied platelet function and bone marrow (BM) features in five GPS patients with NBEAL2 autosomal recessive mutations from four unrelated families. In 3/3 patients, we observed a defect in platelet responses to protease-activated receptor (PAR)1-activating peptide as the most consistent finding, either isolated or combined to defective responses to other agonists. A reduction of PAR1 receptors with normal expression of major glycoproteins on the platelet surface was also found. Thrombin-induced fibrinogen binding to platelets was severely impaired in 2/2 patients. In 4/4 patients, the BM biopsy showed fibrosis (grade 2-3) and extensive emperipolesis, with many (36-65%) MKs containing 2-4 leukocytes engulfed within the cytoplasm. Reduced immunolabeling for platelet factor 4 together with normal immunolabeling for CD63 in MKs of two patients demonstrated that GPS MKs display an alpha granule-specific defect. Increased immunolabeling for P-selectin and decreased immunolabeling for PAR1, PAR4 and c-MPL were also observed in MKs of two patients. Marked emperipolesis, specific defect of MK alpha-granule content and defect of PAR1-mediated platelet responses are present in all GPS patients that we could study in detail. These results help to further characterize the disease.
Fil: Larroca, Luigi M.. Policlinico A. Gemelli. Department Of Internal Medicine; 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: Podda, Gianmarco. Medicina Iii, Azienda Ospedaliera San Paolo; Italia
Fil: Pujol Moix, Nuria. Institut de Recerca Sant Pau; España
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. Irccs Policlinico San Matteo Foundation; Italia
Fil: Alberelli, Maria Adele. Policlinico A. Gemelli. Department Of Internal Medicine; Italia
Fil: Balduini, Carlo L.. Policlinico San Matteo. Universidad de Pavia.; Italia
Fil: Landolfi, Raffaele. Università Cattolica del Sacro Cuore; Italia
Fil: Cattaneo, Marco. Azienda Ospedaliera San Paolo, Dipartimento Di Scienze; Italia
Fil: De Candia, Erica. Università Cattolica del Sacro Cuore; Italia
Materia
Emperipolesis
Par1 Receptor
Gray Platelet Syndrome
Megakaryocytes
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38762
Acceder
id CONICETDig_b84a0607aa10ef4760a9fcb13bacb534
oai_identifier_str oai:ri.conicet.gov.ar:11336/38762
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndromeLarroca, Luigi M.Heller, Paula GracielaPodda, GianmarcoPujol Moix, NuriaGlembotsky, Ana ClaudiaPecci, AlessandroAlberelli, Maria AdeleBalduini, Carlo L.Landolfi, RaffaeleCattaneo, MarcoDe Candia, EricaEmperipolesisPar1 ReceptorGray Platelet SyndromeMegakaryocyteshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The gray platelet syndrome (GPS) is a rare congenital platelet disorder characterized by mild to moderate bleeding diathesis, macrothrombocytopenia and lack of azurophilic α-granules in platelets. Some platelet and megakaryocyte (MK) abnormalities have been described, but confirmative studies of the defects in larger patient cohorts have not been undertaken. We studied platelet function and bone marrow (BM) features in five GPS patients with NBEAL2 autosomal recessive mutations from four unrelated families. In 3/3 patients, we observed a defect in platelet responses to protease-activated receptor (PAR)1-activating peptide as the most consistent finding, either isolated or combined to defective responses to other agonists. A reduction of PAR1 receptors with normal expression of major glycoproteins on the platelet surface was also found. Thrombin-induced fibrinogen binding to platelets was severely impaired in 2/2 patients. In 4/4 patients, the BM biopsy showed fibrosis (grade 2-3) and extensive emperipolesis, with many (36-65%) MKs containing 2-4 leukocytes engulfed within the cytoplasm. Reduced immunolabeling for platelet factor 4 together with normal immunolabeling for CD63 in MKs of two patients demonstrated that GPS MKs display an alpha granule-specific defect. Increased immunolabeling for P-selectin and decreased immunolabeling for PAR1, PAR4 and c-MPL were also observed in MKs of two patients. Marked emperipolesis, specific defect of MK alpha-granule content and defect of PAR1-mediated platelet responses are present in all GPS patients that we could study in detail. These results help to further characterize the disease.Fil: Larroca, Luigi M.. Policlinico A. Gemelli. Department Of Internal Medicine; ItaliaFil: 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; ArgentinaFil: Podda, Gianmarco. Medicina Iii, Azienda Ospedaliera San Paolo; ItaliaFil: Pujol Moix, Nuria. Institut de Recerca Sant Pau; EspañaFil: 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; ArgentinaFil: Pecci, Alessandro. Irccs Policlinico San Matteo Foundation; ItaliaFil: Alberelli, Maria Adele. Policlinico A. Gemelli. Department Of Internal Medicine; ItaliaFil: Balduini, Carlo L.. Policlinico San Matteo. Universidad de Pavia.; ItaliaFil: Landolfi, Raffaele. Università Cattolica del Sacro Cuore; ItaliaFil: Cattaneo, Marco. Azienda Ospedaliera San Paolo, Dipartimento Di Scienze; ItaliaFil: De Candia, Erica. Università Cattolica del Sacro Cuore; ItaliaTaylor & Francis Ltd2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38762Larroca, Luigi M.; Heller, Paula Graciela; Podda, Gianmarco; Pujol Moix, Nuria; Glembotsky, Ana Claudia; et al.; Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome; Taylor & Francis Ltd; Platelets; 26; 8; 2015; 751-7570953-71041369-1635CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3109/09537104.2014.994093info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.3109/09537104.2014.994093info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:00Zoai:ri.conicet.gov.ar:11336/38762instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:00.969CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome
title Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome
spellingShingle Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome
Larroca, Luigi M.
Emperipolesis
Par1 Receptor
Gray Platelet Syndrome
Megakaryocytes
title_short Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome
title_full Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome
title_fullStr Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome
title_full_unstemmed Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome
title_sort Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome
dc.creator.none.fl_str_mv Larroca, Luigi M.
Heller, Paula Graciela
Podda, Gianmarco
Pujol Moix, Nuria
Glembotsky, Ana Claudia
Pecci, Alessandro
Alberelli, Maria Adele
Balduini, Carlo L.
Landolfi, Raffaele
Cattaneo, Marco
De Candia, Erica
author Larroca, Luigi M.
author_facet Larroca, Luigi M.
Heller, Paula Graciela
Podda, Gianmarco
Pujol Moix, Nuria
Glembotsky, Ana Claudia
Pecci, Alessandro
Alberelli, Maria Adele
Balduini, Carlo L.
Landolfi, Raffaele
Cattaneo, Marco
De Candia, Erica
author_role author
author2 Heller, Paula Graciela
Podda, Gianmarco
Pujol Moix, Nuria
Glembotsky, Ana Claudia
Pecci, Alessandro
Alberelli, Maria Adele
Balduini, Carlo L.
Landolfi, Raffaele
Cattaneo, Marco
De Candia, Erica
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Emperipolesis
Par1 Receptor
Gray Platelet Syndrome
Megakaryocytes
topic Emperipolesis
Par1 Receptor
Gray Platelet Syndrome
Megakaryocytes
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The gray platelet syndrome (GPS) is a rare congenital platelet disorder characterized by mild to moderate bleeding diathesis, macrothrombocytopenia and lack of azurophilic α-granules in platelets. Some platelet and megakaryocyte (MK) abnormalities have been described, but confirmative studies of the defects in larger patient cohorts have not been undertaken. We studied platelet function and bone marrow (BM) features in five GPS patients with NBEAL2 autosomal recessive mutations from four unrelated families. In 3/3 patients, we observed a defect in platelet responses to protease-activated receptor (PAR)1-activating peptide as the most consistent finding, either isolated or combined to defective responses to other agonists. A reduction of PAR1 receptors with normal expression of major glycoproteins on the platelet surface was also found. Thrombin-induced fibrinogen binding to platelets was severely impaired in 2/2 patients. In 4/4 patients, the BM biopsy showed fibrosis (grade 2-3) and extensive emperipolesis, with many (36-65%) MKs containing 2-4 leukocytes engulfed within the cytoplasm. Reduced immunolabeling for platelet factor 4 together with normal immunolabeling for CD63 in MKs of two patients demonstrated that GPS MKs display an alpha granule-specific defect. Increased immunolabeling for P-selectin and decreased immunolabeling for PAR1, PAR4 and c-MPL were also observed in MKs of two patients. Marked emperipolesis, specific defect of MK alpha-granule content and defect of PAR1-mediated platelet responses are present in all GPS patients that we could study in detail. These results help to further characterize the disease.
Fil: Larroca, Luigi M.. Policlinico A. Gemelli. Department Of Internal Medicine; 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: Podda, Gianmarco. Medicina Iii, Azienda Ospedaliera San Paolo; Italia
Fil: Pujol Moix, Nuria. Institut de Recerca Sant Pau; España
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. Irccs Policlinico San Matteo Foundation; Italia
Fil: Alberelli, Maria Adele. Policlinico A. Gemelli. Department Of Internal Medicine; Italia
Fil: Balduini, Carlo L.. Policlinico San Matteo. Universidad de Pavia.; Italia
Fil: Landolfi, Raffaele. Università Cattolica del Sacro Cuore; Italia
Fil: Cattaneo, Marco. Azienda Ospedaliera San Paolo, Dipartimento Di Scienze; Italia
Fil: De Candia, Erica. Università Cattolica del Sacro Cuore; Italia
description The gray platelet syndrome (GPS) is a rare congenital platelet disorder characterized by mild to moderate bleeding diathesis, macrothrombocytopenia and lack of azurophilic α-granules in platelets. Some platelet and megakaryocyte (MK) abnormalities have been described, but confirmative studies of the defects in larger patient cohorts have not been undertaken. We studied platelet function and bone marrow (BM) features in five GPS patients with NBEAL2 autosomal recessive mutations from four unrelated families. In 3/3 patients, we observed a defect in platelet responses to protease-activated receptor (PAR)1-activating peptide as the most consistent finding, either isolated or combined to defective responses to other agonists. A reduction of PAR1 receptors with normal expression of major glycoproteins on the platelet surface was also found. Thrombin-induced fibrinogen binding to platelets was severely impaired in 2/2 patients. In 4/4 patients, the BM biopsy showed fibrosis (grade 2-3) and extensive emperipolesis, with many (36-65%) MKs containing 2-4 leukocytes engulfed within the cytoplasm. Reduced immunolabeling for platelet factor 4 together with normal immunolabeling for CD63 in MKs of two patients demonstrated that GPS MKs display an alpha granule-specific defect. Increased immunolabeling for P-selectin and decreased immunolabeling for PAR1, PAR4 and c-MPL were also observed in MKs of two patients. Marked emperipolesis, specific defect of MK alpha-granule content and defect of PAR1-mediated platelet responses are present in all GPS patients that we could study in detail. These results help to further characterize the disease.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/38762
Larroca, Luigi M.; Heller, Paula Graciela; Podda, Gianmarco; Pujol Moix, Nuria; Glembotsky, Ana Claudia; et al.; Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome; Taylor & Francis Ltd; Platelets; 26; 8; 2015; 751-757
0953-7104
1369-1635
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38762
identifier_str_mv Larroca, Luigi M.; Heller, Paula Graciela; Podda, Gianmarco; Pujol Moix, Nuria; Glembotsky, Ana Claudia; et al.; Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome; Taylor & Francis Ltd; Platelets; 26; 8; 2015; 751-757
0953-7104
1369-1635
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3109/09537104.2014.994093
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.3109/09537104.2014.994093
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis Ltd
publisher.none.fl_str_mv Taylor & Francis Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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