Modifying platelets at their birth: anti-thrombotic therapy without haemorrhage

Cardiovascular disease is a leading cause of death. The current approach to the prevention of arterial thrombosis in cardiovascular disease is dependent on the use of therapies which inhibit the activation of platelets. Predictably these are associated with an increased risk of haemorrhage which cau...

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Main Authors: Conor Feely, Nitika Kaushal, Pier Paolo D’Avino, John Martin
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1343896/full
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author Conor Feely
Nitika Kaushal
Pier Paolo D’Avino
John Martin
John Martin
author_facet Conor Feely
Nitika Kaushal
Pier Paolo D’Avino
John Martin
John Martin
author_sort Conor Feely
collection DOAJ
description Cardiovascular disease is a leading cause of death. The current approach to the prevention of arterial thrombosis in cardiovascular disease is dependent on the use of therapies which inhibit the activation of platelets. Predictably these are associated with an increased risk of haemorrhage which causes significant morbidity. The thrombotic potential of an activated platelet is modifiable; being determined before thrombopoiesis. Increased megakaryocyte ploidy is associated with larger and more active platelets carrying an increased risk of thrombosis. The reduction in the ploidy of megakaryocytes is therefore a novel area of therapeutic interest for reducing thrombosis. We propose a new therapeutic approach for the prevention and treatment of thrombosis by targeting the reduction in ploidy of megakaryocytes. We examine the role of a receptor mediated event causing megakaryocytes to increase ploidy, the potential for targeting the molecular mechanisms underpinning megakaryocyte endomitosis and the existence of two separate regulatory pathways to maintain haemostasis by altering the thrombotic potential of platelets as targets for novel therapeutic approaches producing haemostatically competent platelets which are not prothrombotic.
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spelling doaj.art-2a4bf069b8ad4842b8af9cecaa8724162024-03-18T04:43:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.13438961343896Modifying platelets at their birth: anti-thrombotic therapy without haemorrhageConor Feely0Nitika Kaushal1Pier Paolo D’Avino2John Martin3John Martin4Centre for Clinical Pharmacology, Institute of Health Informatics, University College London, London, United KingdomCentre for Clinical Pharmacology, Institute of Health Informatics, University College London, London, United KingdomDepartment of Pathology, University of Cambridge, Cambridge, United KingdomCentre for Clinical Pharmacology, Institute of Health Informatics, University College London, London, United KingdomDivision of Medicine, University College London, London, United KingdomCardiovascular disease is a leading cause of death. The current approach to the prevention of arterial thrombosis in cardiovascular disease is dependent on the use of therapies which inhibit the activation of platelets. Predictably these are associated with an increased risk of haemorrhage which causes significant morbidity. The thrombotic potential of an activated platelet is modifiable; being determined before thrombopoiesis. Increased megakaryocyte ploidy is associated with larger and more active platelets carrying an increased risk of thrombosis. The reduction in the ploidy of megakaryocytes is therefore a novel area of therapeutic interest for reducing thrombosis. We propose a new therapeutic approach for the prevention and treatment of thrombosis by targeting the reduction in ploidy of megakaryocytes. We examine the role of a receptor mediated event causing megakaryocytes to increase ploidy, the potential for targeting the molecular mechanisms underpinning megakaryocyte endomitosis and the existence of two separate regulatory pathways to maintain haemostasis by altering the thrombotic potential of platelets as targets for novel therapeutic approaches producing haemostatically competent platelets which are not prothrombotic.https://www.frontiersin.org/articles/10.3389/fphar.2024.1343896/fullmegakaryocyteplateletthrombosistherapeuticsploidy
spellingShingle Conor Feely
Nitika Kaushal
Pier Paolo D’Avino
John Martin
John Martin
Modifying platelets at their birth: anti-thrombotic therapy without haemorrhage
Frontiers in Pharmacology
megakaryocyte
platelet
thrombosis
therapeutics
ploidy
title Modifying platelets at their birth: anti-thrombotic therapy without haemorrhage
title_full Modifying platelets at their birth: anti-thrombotic therapy without haemorrhage
title_fullStr Modifying platelets at their birth: anti-thrombotic therapy without haemorrhage
title_full_unstemmed Modifying platelets at their birth: anti-thrombotic therapy without haemorrhage
title_short Modifying platelets at their birth: anti-thrombotic therapy without haemorrhage
title_sort modifying platelets at their birth anti thrombotic therapy without haemorrhage
topic megakaryocyte
platelet
thrombosis
therapeutics
ploidy
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1343896/full
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AT johnmartin modifyingplateletsattheirbirthantithrombotictherapywithouthaemorrhage
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