Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model

Current cytoreductive and antithrombotic strategies in MPNs are mostly based on cell counts and on patient’s demographic and clinical history. Despite the numerous studies conducted on platelet function and on the role of plasma factors, an accurate and reliable method to dynamically quantify the hy...

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Autores principales:	Alessandro Lucchesi, Roberta Napolitano, Maria Teresa Bochicchio, Giulio Giordano, Mariasanta Napolitano
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MPN platelet function thrombin generation PAR receptors fibrinogen Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/32c1720eb50546968774fa84b741cc2f
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spelling	oai:doaj.org-article:32c1720eb50546968774fa84b741cc2f2021-11-11T16:49:18ZPlatelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model10.3390/ijms2221113431422-00671661-6596https://doaj.org/article/32c1720eb50546968774fa84b741cc2f2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11343https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Current cytoreductive and antithrombotic strategies in MPNs are mostly based on cell counts and on patient’s demographic and clinical history. Despite the numerous studies conducted on platelet function and on the role of plasma factors, an accurate and reliable method to dynamically quantify the hypercoagulability states of these conditions is not yet part of clinical practice. Starting from our experience, and after having sifted through the literature, we propose an in-depth narrative report on the contribution of the clonal platelets of MPNs—rich in tissue factor (TF)—in promoting a perpetual procoagulant mechanism. The whole process results in an unbalanced generation of thrombin and is self-maintained by Protease Activated Receptors (PARs). We chose to define this model as a “circulating wound”, as it indisputably links the coagulation, inflammation, and fibrotic progression of the disease, in analogy with what happens in some solid tumours. The platelet contribution to thrombin generation results in triggering a vicious circle supported by the PARs/TGF-beta axis. PAR antagonists could therefore be a good option for target therapy, both to contain the risk of vascular events and to slow the progression of the disease towards end-stage forms. Both the new and old strategies, however, will require tools capable of measuring procoagulant or prohaemorrhagic states in a more extensive and dynamic way to favour a less empirical management of MPNs and their potential clinical complications.Alessandro LucchesiRoberta NapolitanoMaria Teresa BochicchioGiulio GiordanoMariasanta NapolitanoMDPI AGarticleMPNplatelet functionthrombin generationPAR receptorsfibrinogenBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11343, p 11343 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MPN platelet function thrombin generation PAR receptors fibrinogen Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	MPN platelet function thrombin generation PAR receptors fibrinogen Biology (General) QH301-705.5 Chemistry QD1-999 Alessandro Lucchesi Roberta Napolitano Maria Teresa Bochicchio Giulio Giordano Mariasanta Napolitano Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model
description	Current cytoreductive and antithrombotic strategies in MPNs are mostly based on cell counts and on patient’s demographic and clinical history. Despite the numerous studies conducted on platelet function and on the role of plasma factors, an accurate and reliable method to dynamically quantify the hypercoagulability states of these conditions is not yet part of clinical practice. Starting from our experience, and after having sifted through the literature, we propose an in-depth narrative report on the contribution of the clonal platelets of MPNs—rich in tissue factor (TF)—in promoting a perpetual procoagulant mechanism. The whole process results in an unbalanced generation of thrombin and is self-maintained by Protease Activated Receptors (PARs). We chose to define this model as a “circulating wound”, as it indisputably links the coagulation, inflammation, and fibrotic progression of the disease, in analogy with what happens in some solid tumours. The platelet contribution to thrombin generation results in triggering a vicious circle supported by the PARs/TGF-beta axis. PAR antagonists could therefore be a good option for target therapy, both to contain the risk of vascular events and to slow the progression of the disease towards end-stage forms. Both the new and old strategies, however, will require tools capable of measuring procoagulant or prohaemorrhagic states in a more extensive and dynamic way to favour a less empirical management of MPNs and their potential clinical complications.
format	article
author	Alessandro Lucchesi Roberta Napolitano Maria Teresa Bochicchio Giulio Giordano Mariasanta Napolitano
author_facet	Alessandro Lucchesi Roberta Napolitano Maria Teresa Bochicchio Giulio Giordano Mariasanta Napolitano
author_sort	Alessandro Lucchesi
title	Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model
title_short	Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model
title_full	Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model
title_fullStr	Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model
title_full_unstemmed	Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model
title_sort	platelets contribution to thrombin generation in philadelphia-negative myeloproliferative neoplasms: the “circulating wound” model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/32c1720eb50546968774fa84b741cc2f
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Platelets Contribution to Thrombin Generation in Philadelphia-Negative Myeloproliferative Neoplasms: The “Circulating Wound” Model

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