Flow studies on human GPVI-deficient blood under coagulating and noncoagulating conditions

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dc.catalogadoryvc
dc.contributor.authorNagy, Magdolna
dc.contributor.authorPerrella, Gina
dc.contributor.authorDalby, Amanda
dc.contributor.authorBecerra Yañez, María Francisca Aurora del Car
dc.contributor.authorGarcía Quintanilla, Lourdes
dc.contributor.authorPike, Jeremy A.
dc.contributor.authorMorgan, Neil V.
dc.contributor.authorGardiner, Elizabeth E.
dc.contributor.authorHeemskerk, Johan W. M.
dc.contributor.authorAzócar López, Lorena Karina
dc.contributor.authorMiquel Poblete, Juan Francisco
dc.contributor.authorMezzano Abedrapo, Diego
dc.contributor.authorWatson, Steve P.
dc.date.accessioned2024-08-08T22:11:19Z
dc.date.available2024-08-08T22:11:19Z
dc.date.issued2020
dc.description.abstractThe role of glycoprotein VI (GPVI) in platelets was investigated in 3 families bearing an insertion within the GP6 gene that introduces a premature stop codon prior to the transmembrane domain, leading to expression of a truncated protein in the cytoplasm devoid of the transmembrane region. Western blotting and flow cytometry of GP6(hom) (homozygous) platelets confirmed loss of the full protein. The level of the Fc receptor -gamma-chain, which associates with GPVI in the membrane, was partially reduced, but expression of other receptors and signaling proteins was not altered. Spreading of platelets on collagen and von Willebrand factor (which supports partial spreading) was abolished in GP6(hom) platelets, and spreading on uncoated glass was reduced. Anticoagulated whole blood flowed over immobilized collagen or a mixture of von Willebrand factor, laminin, and rhodocytin (noncollagen surface) generated stable platelet aggregates that express phosphatidylserine (PS). Both responses were blocked on the 2 surfaces in GP6(hom) individuals, but adhesion was not altered. Thrombin generation was partially reduced in GP6(hom) blood. The frequency of the GP6(het) (heterozygous) variant in a representative sample of the Chilean population (1212 donors) is 2.9%, indicating that there are similar to 4000 GP6(hom) individuals in Chile. These results demonstrate that GPVI supports aggregation and PS exposure under flow on collagen and noncollagen surfaces, but not adhesion. The retention of adhesion may contribute to the mild bleeding diathesis of GP6(hom) patients and account for why so few of the estimated 4000 GP6(hom) individuals in Chile have been identified.
dc.fechaingreso.objetodigital2024-08-05
dc.fuente.origenConveris
dc.identifier.converisid1
dc.identifier.doi10.1182/bloodadvances.2020001761
dc.identifier.issn2473-9529
dc.identifier.pubmedidMedline ID: 32603422
dc.identifier.scopusidScopus_ID: 2-s2.0-85088376946
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87381
dc.identifier.wosidWoS_ID:000551200600012
dc.information.autorucEscuela de Medicina; Becerra Yañez, María Francisca Aurora del Car; S/I; 187021
dc.information.autorucS/I; Azócar López, Lorena Karina; S/I; 1006324
dc.information.autorucEscuela de Medicina; Miquel Poblete, Juan Francisco; 0000-0002-0526-4377; 72216
dc.information.autorucEscuela de Medicina; Mezzano Abedrapo, Diego; 0000-0003-2448-9288; 99455
dc.issue.numero13
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final2961
dc.pagina.inicio2953
dc.revistaBlood Advances
dc.rightsacceso restringido
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleFlow studies on human GPVI-deficient blood under coagulating and noncoagulating conditions
dc.typeartículo
dc.volumen4
sipa.codpersvinculados187021
sipa.codpersvinculados1006324
sipa.codpersvinculados72216
sipa.codpersvinculados99455
sipa.trazabilidadConveris;20-07-2021
sipa.trazabilidadORCID;2024-08-05
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