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Platelet activation in heparin-induced thrombocytopenia is followed by platelet death via complex apoptotic and non-apoptotic pathways

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dc.contributor.author Mordakhanova E.R.
dc.contributor.author Nevzorova T.A.
dc.contributor.author Synbulatova G.E.
dc.contributor.author Rauova L.
dc.contributor.author Weisel J.W.
dc.contributor.author Litvinov R.I.
dc.date.accessioned 2021-02-25T20:44:41Z
dc.date.available 2021-02-25T20:44:41Z
dc.date.issued 2020
dc.identifier.issn 1661-6596
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/162361
dc.description.abstract © 2020 by the authors. Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction characterized by thrombocytopenia and a high risk for venous or arterial thrombosis. HIT is caused by antibodies that recognize complexes of platelet factor 4 and heparin. The pathogenic mechanisms of this condition are not fully understood. In this study, we used flow cytometry, fluorimetry, and Western blot analysis to study the direct effects of pathogenic immune complexes containing platelet factor 4 on human platelets isolated by gel-filtration. HIT-like pathogenic immune complexes initially caused pronounced activation of platelets detected by an increased expression of phosphatidylserine and P-selectin. This activation was mediated either directly through the FcγRIIA receptors or indirectly via protease-activated receptor 1 (PAR1) receptors due to thrombin generated on or near the surface of activated platelets. The immune activation was later followed by the biochemical signs of cell death, such as mitochondrial membrane depolarization, up-regulation of Bax, down-regulation of Bcl-XL, and moderate activation of procaspase 3 and increased calpain activity. The results show that platelet activation under the action of HIT-like immune complexes is accompanied by their death through complex apoptotic and calpain-dependent non-apoptotic pathways that may underlie the low platelet count in HIT.
dc.relation.ispartofseries International Journal of Molecular Sciences
dc.subject Apoptosis
dc.subject Calpain
dc.subject Caspase
dc.subject Heparin-induced thrombocytopenia
dc.subject Platelet death
dc.subject Platelets
dc.title Platelet activation in heparin-induced thrombocytopenia is followed by platelet death via complex apoptotic and non-apoptotic pathways
dc.type Article
dc.relation.ispartofseries-issue 7
dc.relation.ispartofseries-volume 21
dc.collection Публикации сотрудников КФУ
dc.source.id SCOPUS16616596-2020-21-7-SID85083196740


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  • Публикации сотрудников КФУ Scopus [24551]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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