Platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombin

Abstract Thrombosis is one of the cardinal manifestations of myeloproliferative neoplasms (MPN). The mechanisms leading to a prothrombotic state in MPN are complex and remain poorly understood. Platelet mitochondria play a role in platelet activation, but their number and function have not been exte...

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Main Authors: David M. Ross, Hai Po Helena Liang, Zeenet Iqra, Shane Whittaker, Chuen Wen Tan, Brian J. Dale, Vivien M. Chen
Format: Article
Language:English
Published: Nature Portfolio 2023-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-36266-2
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author David M. Ross
Hai Po Helena Liang
Zeenet Iqra
Shane Whittaker
Chuen Wen Tan
Brian J. Dale
Vivien M. Chen
author_facet David M. Ross
Hai Po Helena Liang
Zeenet Iqra
Shane Whittaker
Chuen Wen Tan
Brian J. Dale
Vivien M. Chen
author_sort David M. Ross
collection DOAJ
description Abstract Thrombosis is one of the cardinal manifestations of myeloproliferative neoplasms (MPN). The mechanisms leading to a prothrombotic state in MPN are complex and remain poorly understood. Platelet mitochondria play a role in platelet activation, but their number and function have not been extensively explored in MPN to date. We observed an increased number of mitochondria in platelets from MPN patients compared with healthy donors. MPN patients had an increased proportion of dysfunctional platelet mitochondria. The fraction of platelets with depolarized mitochondria at rest was increased in essential thrombocythemia (ET) patients and the mitochondria were hypersensitive to depolarization following thrombin agonist stimulation. Live microscopy showed a stochastic process in which a higher proportion of individual ET platelets underwent mitochondrial depolarization and after a shorter agonist exposure compared to healthy donors. Depolarization was immediately followed by ballooning of the platelet membrane, which is a feature of procoagulant platelets. We also noted that the mitochondria of MPN patients were on average located nearer the platelet surface and we observed extrusion of mitochondria from the platelet surface as microparticles. These data implicate platelet mitochondria in a number of prothrombotic phenomena. Further studies are warranted to assess whether these findings correlate with clinical thrombotic events.
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spelling doaj.art-0c2dc6f9f36947d8b37f2cf037a187262023-06-11T11:12:39ZengNature PortfolioScientific Reports2045-23222023-06-0113111410.1038/s41598-023-36266-2Platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombinDavid M. Ross0Hai Po Helena Liang1Zeenet Iqra2Shane Whittaker3Chuen Wen Tan4Brian J. Dale5Vivien M. Chen6Centre for Cancer Biology, SA Pathology and University of South AustraliaANZAC Research Institute, Concord Repatriation General HospitalClinical and Health Sciences, University of South AustraliaANZAC Research Institute, Concord Repatriation General HospitalANZAC Research Institute, Concord Repatriation General HospitalClinical and Health Sciences, University of South AustraliaANZAC Research Institute, Concord Repatriation General HospitalAbstract Thrombosis is one of the cardinal manifestations of myeloproliferative neoplasms (MPN). The mechanisms leading to a prothrombotic state in MPN are complex and remain poorly understood. Platelet mitochondria play a role in platelet activation, but their number and function have not been extensively explored in MPN to date. We observed an increased number of mitochondria in platelets from MPN patients compared with healthy donors. MPN patients had an increased proportion of dysfunctional platelet mitochondria. The fraction of platelets with depolarized mitochondria at rest was increased in essential thrombocythemia (ET) patients and the mitochondria were hypersensitive to depolarization following thrombin agonist stimulation. Live microscopy showed a stochastic process in which a higher proportion of individual ET platelets underwent mitochondrial depolarization and after a shorter agonist exposure compared to healthy donors. Depolarization was immediately followed by ballooning of the platelet membrane, which is a feature of procoagulant platelets. We also noted that the mitochondria of MPN patients were on average located nearer the platelet surface and we observed extrusion of mitochondria from the platelet surface as microparticles. These data implicate platelet mitochondria in a number of prothrombotic phenomena. Further studies are warranted to assess whether these findings correlate with clinical thrombotic events.https://doi.org/10.1038/s41598-023-36266-2
spellingShingle David M. Ross
Hai Po Helena Liang
Zeenet Iqra
Shane Whittaker
Chuen Wen Tan
Brian J. Dale
Vivien M. Chen
Platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombin
Scientific Reports
title Platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombin
title_full Platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombin
title_fullStr Platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombin
title_full_unstemmed Platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombin
title_short Platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombin
title_sort platelets from patients with myeloproliferative neoplasms have increased numbers of mitochondria that are hypersensitive to depolarization by thrombin
url https://doi.org/10.1038/s41598-023-36266-2
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