Review
Biochemistry & Molecular Biology
Alina Scridon
Summary: This article comprehensively explores the complex role of platelets in hemostasis and thrombosis, discussing their importance in clinical medicine, and studying hemostatic platelet-related disorders and antithrombotic therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Oliver Borst, Meinrad Gawaz
Summary: Subendothelial collagen exposed to platelets after rupture of atherosclerotic plaques is the main trigger of platelet activation and acute arterial thrombotic occlusion. Developing antiplatelet strategies that selectively inhibit atherothrombosis without interfering with bleeding control is an unmet clinical need. Platelet glycoprotein VI (GPVI) plays a crucial role in collagen-induced platelet activation and aggregation, making it a potential target for novel therapeutic strategies in thrombotic and inflammatory diseases.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Immunology
Xiang Chu, Jie Zhang, Yingying Li, Ke Yuan, Xue Wang, Xiang Gui, Yueyue Sun, Chaonan Geng, Wen Ju, Mengdi Xu, Zhenyu Li, Lingyu Zeng, Kailin Xu, Jianlin Qiao
Summary: This study aimed to evaluate the effect of Dimethyl fumarate (DMF) on platelet function. The results showed that DMF significantly inhibited platelet aggregation and granule release, reduced platelet spreading and clot retraction, and prolonged bleeding time in mice. Furthermore, DMF also reduced the generation of reactive oxygen species and inhibited NF-κB activation and phosphorylation of ERK1/2, p38 and AKT. Overall, DMF inhibits platelet function and thrombus formation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maan H. Harbi, Christopher W. Smith, Fawaz O. Alenazy, Phillip L. R. Nicolson, Alok Tiwari, Steve P. Watson, Mark R. Thomas
Summary: The study investigates the effect of Syk inhibitor fostamatinib as an antiplatelet drug, showing that it mildly inhibits platelet responses induced by atherosclerotic plaque and that this effect is amplified by aspirin and ticagrelor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Sukhdeep Bhogal, Ron Waksman, Paul Gordon, Afshin Ehsan, Sean R. Wilson, Robert Levitt, Puja Parikh, Thomas Bilfinger, Nicholas Hanna, Maurice Buchbinder, Federico M. Asch, Gaby Weissman, Itsik Ben-Dor, Christian C. Shults, Syed Ali, Corey Shea, Cheng Zhang, Hector M. Garcia-Garcia, Lowell F. Satler, Toby Rogers
Summary: This study evaluated the impact of antithrombotic regimens on subclinical leaflet thrombosis (SLT) in low-risk patients who underwent transcatheter aortic valve implantation (TAVI). The results showed that oral anticoagulation was associated with significantly lower rates of SLT at 30 days compared to dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT), and there was no apparent benefit of DAPT over SAPT. Additionally, short-term oral anticoagulation did not increase bleeding risk compared to SAPT or DAPT.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Article
Immunology
Freda H. Passam, Gang Chen, Vivien M. Chen, Miao Qi, Steven A. Krilis, Bill Giannakopoulos
Summary: This study found that ss2GPI deficient mice have enhanced thrombus formation compared to wild type mice, and the antithrombotic function of ss2GPI is mainly dependent on its fifth domain.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Hematology
David S. Paul, Tasha N. Blatt, Wyatt J. Schug, Emily G. Clark, Tomohiro Kawano, Nigel Mackman, Sebastian Murcia, Kathryn O. Poe, Jean Marie N. Mwiza, T. Kendall Harden, Wolfgang Bergmeier, Robert A. Nicholas
Summary: Rapid desensitization of the P2Y1 receptor plays a critical role in platelet function and thrombus formation, but does not affect platelet adhesion and aggregation at sites of vascular injury.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Masaaki Moroi, Isuru Induruwa, Richard W. Farndale, Stephanie M. Jung
Summary: The study found that dimeric GPVI acts as the receptor for fibrin, with different binding affinities to noncrosslinked and crosslinked fibrin clots. Its binding kinetics are similar to those obtained for binding to fibrinogen D-fragment and D-dimer, suggesting that the GPVI-binding site on fibrin(ogen) becomes exposed after fibrin formation or cleavage. Analysis of platelets bound to fibrin clots indicates that platelet GPVI binds to fibrin fibers comprising the clot.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Review
Biochemistry & Molecular Biology
Natasha M. Setiabakti, Pia Larsson, Justin R. Hamilton
Summary: Understanding the role of phosphoinositide 3-kinases (PI3Ks) in platelet function and thrombus formation is crucial for the development of therapeutic drugs for thrombotic cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Luis Ortega-Paz, Davide Capodanno, Gilles Montalescot, Dominick J. Angiolillo
Summary: COVID-19 caused by severe acute respiratory syndrome coronavirus-2 can lead to intense inflammatory and prothrombotic states, with cardiovascular implications and an increased risk of thrombotic events. The virus utilizes angiotensin-converting enzyme 2 as a functional receptor, which is highly expressed in the respiratory and cardiovascular systems.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Review
Hematology
Errol W. Aarnink, Marina F. M. Huijboom, Willem L. Bor, Moniek Maarse, Kai L. Zheng, Hugo Ten Cate, Jurrien M. Ten Berg, Lucas V. A. Boersma
Summary: Atrial septal defect, persistent foramen ovale, and left atrial appendage can now be closed percutaneously using implantable devices. However, these interventions may lead to thromboembolic events, and the optimal post-procedural antithrombotic management is still uncertain. The mechanisms behind device-related thrombus and thromboembolic complications are not fully understood, but biomarkers of coagulation activation increase while platelet reactivity remains unchanged. This suggests that a regimen including anticoagulation therapy may be more effective than the current antiplatelet-based approach.
THROMBOSIS RESEARCH
(2022)
Review
Cardiac & Cardiovascular Systems
Gauranga Mahalwar, Ashish Kumar, Monil Majmundar, Olayinka Adebolu, Revanth Yendamuri, Nicole Lao, Nishad Barve, Rolf P. Kreutz, Grant W. Reed, Rishi Puri, Sourbha S. Dani, Ankur Kalra
Summary: The optimal antithrombotic therapy post transcatheter aortic valve replacement (TAVR) remains uncertain. A network meta-analysis of randomized controlled trials was conducted to determine the outcomes with various antithrombotic strategies. The results showed that single antiplatelet therapy (SAPT) was associated with a reduced risk of major or life-threatening bleeding compared to dual antiplatelet therapy (DAPT). Other antithrombotic strategies had similar odds of major and life-threatening bleeding compared to DAPT. There were no differences in the incidence of stroke, myocardial infarction, all-cause mortality, and cardiac mortality among the various antithrombotic strategies post TAVR.
CURRENT PROBLEMS IN CARDIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Martha M. S. Sim, Semekidus Shiferawe, Jeremy P. Wood
Summary: Antithrombotic therapy requires balancing the benefits of preventing thrombotic events with the risks of major bleeds. Traditional approaches involve carefully dosing and monitoring antiplatelet and anticoagulant medications, all of which carry bleeding risk. Recent advancements have identified new targets to mitigate bleeding risk. This review discusses the current state of antithrombotic therapy and explores new generation drugs and strategies to reverse anticoagulants, moving closer to a treatment that prevents clots without bleeding risk.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Lifeng Luo, Zhong Chen, Tong Gong, Qingsong Ye, Hao Li, Yunfei Guo, Jiqiu Wen, Yiqiao Hu, Jinhui Wu
Summary: Thrombosis is a major global health issue. Traditional antiplatelet therapy interferes with platelet activation and carries a risk of bleeding. However, a new approach using cytosolic delivery of nanoscale perfluorocarbon (PFC) via albumin has been developed, which inhibits platelet function without interfering with platelet activation through integrin alpha IIb beta 3. This novel antiplatelet method has shown potential effectiveness and lower bleeding risk in preventing thrombosis in various models.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Biochemistry & Molecular Biology
Luigi Falco, Viviana Tessitore, Giovanni Ciccarelli, Marco Malvezzi, Antonello D'Andrea, Egidio Imbalzano, Paolo Golino, Vincenzo Russo
Summary: Thrombosis-related diseases are a major cause of illness and death, despite advances in pharmacologic therapy. Oxidative stress plays a crucial role in thrombosis pathophysiology. Anticoagulant and antiplatelet drugs used in the management of these diseases have pleiotropic effects, including antioxidant effects. This review aims to summarize the current evidence on the antioxidant effects of oral antithrombotic therapies in patients with atherosclerotic disease and atrial fibrillation.
Article
Cell Biology
Francois Delvoye, Stephane Loyau, Julien Labreuche, Guillaume Taylor, Benjamin Maier, Michel Piotin, Raphael Blanc, Simon Escalard, Lucas Di Meglio, Malek Ben Maacha, Hocine Redjem, Stanislas Smajda, Gabriele Ciccio, Solene Hebert, Candice Sabben, Martine Jandrot-Perrus, Alain Maertens De Noordhout, Mikael Mazighi, Benoit Ho-Tin-Noe, Jean-Philippe Desilles
Summary: This study investigated the use of the glycoprotein IIb/IIIa antagonist abciximab in treating immediate reocclusion after mechanical thrombectomy for acute ischemic stroke. The results showed that abciximab treatment led to higher recanalization rates without increasing bleeding complications. In vitro experiments further demonstrated that abciximab effectively limits thrombus accretion by blocking platelet aggregation.
Editorial Material
Hematology
Alexandre Slater, Martine Jandrot-Perrus
Summary: The authors of this study report the structure of platelet glycoprotein VI complexed with collagen-related peptides and propose the structural basis of GPVI clustering on collagen fibers.
Article
Clinical Neurology
Raoul Pop, Francois Severac, Anca Hasiu, Dan Mihoc, Pierre H. Mangin, Salvatore Chibbaro, Mihaela Simu, Raluca Tudor, Roxana Gheoca, Veronique Quenardelle, Valerie Wolff, Remy Beaujeux
Summary: An aggressive periprocedural antiplatelet strategy can improve stent patency and clinical outcomes in emergent carotid stenting without increasing the risk of hemorrhagic transformation.
INTERVENTIONAL NEURORADIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Isabella Gizzi Jiacomini, Martina Beltramino, Fanny Boursin, Joao Carlos Minozzo, Juliana Ferreira de Moura, Philippe Billiald, Larissa Magalhaes Alvarenga, Nicolas Aubrey
Summary: The use of monoclonal antibodies in therapy is expanding, with focus on safety, cost-effectiveness, and efficacy. Recombinant DNA technology is used for large-scale production, and strategies for humanization have been developed considering their heterologous origin and potential immunogenicity. This study introduced a mouse monoclonal antibody with binding and neutralizing abilities against spider venom toxins, and explored its humanization potential.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Ilaria De Simone, Constance C. F. M. J. Baaten, Martine Jandrot-Perrus, Jonathan M. Gibbins, Hugo ten Cate, Johan W. M. Heemskerk, Chris Jones, Paola E. J. van der Meijden
Summary: Platelet and coagulation activation are reciprocal processes, and factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Hematology
Emily Janus-Bell, Pierre H. Mangin
Summary: Integrins are transmembrane receptors composed of alpha and beta chains, regulating various cellular functions, including adhesion, migration, proliferation, spreading, and apoptosis. Platelet integrins play a central role in hemostasis by adhesion and aggregation on vascular matrix proteins. Integrins can engage ligands when immobilized, and agonists promote an inside-out signal that increases integrin affinity, reinforcing platelet activation. This review examines the role of platelet integrins in hemostatic plug formation, arterial thrombosis, tumor metastasis, and sepsis.
Article
Hematology
Charles Tacquard, Clarisse Mouriaux, Xavier Delabranche, Catherine Bourdon, Anita Eckly, Stephanie Magnenat, Laurent Sattler, Christian Gachet, Paul Michel Mertes, Beatrice Hechler, Pierre H. Mangin
Summary: Severe COVID-19 is associated with both high rates of thrombotic and bleeding events. Platelet function in these events is uncertain, but this study found that platelets in severe COVID-19 patients showed pre-activation and exhaustion, reduced response to platelet agonists, and decreased adhesion to fibrinogen. The study also suggests that a plasma factor may contribute to the hyporesponsiveness of platelets. These findings highlight the need to carefully evaluate the risks and benefits of high-dose prophylactic anticoagulation in severe COVID-19 patients. Trial registration: ClinicalTrials.gov identifier: NCT04359992.
THROMBOSIS RESEARCH
(2023)
Article
Hematology
Catherine Ang, Catherine Angenieux, Ruch Laurie, Pierre H. Mangin, Christian Gachet, Blandine Maitre
TRANSFUSION MEDICINE
(2023)
Article
Hematology
Philippe Billiald, Alexandre Slater, Martin Welin, Joanne C. Clark, Stephane Loyau, Martine Pugniere, Isabella G. Jiacomini, Nadia Rose, Kristell Lebozec, Elie Toledano, Deborah Francois, Steve P. Watson, Martine Jandrot-Perrus
Summary: This study shows that glenzocimab, a humanized antibody fragment, blocks the binding of GPVI to vascular collagen and fibrin through steric hindrance and structural change. This finding is significant for the development of new antiplatelet molecules with a low bleeding risk.
Article
Neuroimaging
Raoul Pop, Julien Burel, Stephanos Nikolaos Finitsis, Chrysanthi Papagiannaki, Francois Severac, Pierre H. Mangin, Dan Mihoc, Ian Leonard-Lorant, Roxana Gheoca, Valerie Wolff, Salvatore Chibbaro, Igor Sibon, Sebastien Richard, Remy Beaujeux, Gaultier Marnat, Benjamin Gory
Summary: Aggressive antiplatelet treatment is associated with improved intracranial recanalization and carotid stent patency, without safety concerns.
JOURNAL OF NEUROINTERVENTIONAL SURGERY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Esam T. Ahmed Mohamed, Pascal Pomarede, Pierre H. Mangin, Nico F. Declercq
Summary: In this study, sequential measurements of ultrasonic parameters were used to investigate the gradual deteriorations in the biomechanical properties of red blood cells during the preservation period. The findings suggest that ultrasound techniques can be applied as a quick and non-invasive method to check the validity of sealed blood bags. The technique can be used during and beyond the regular preservation period, helping to determine whether to further preserve or withdraw each bag.
BIOMEDICAL PHYSICS & ENGINEERING EXPRESS
(2023)
Review
Hematology
Pierre H. Mangin, Elizabeth E. Gardiner, Robert A. S. Ariens, Martine Jandrot-Perrus
Summary: Platelets, through their engagement with extracellular matrix proteins, are crucial in maintaining hemostasis. The receptor GPVI plays a significant role in platelet biology, mediating platelet/collagen responses and participating in arterial thrombosis. This review focuses on the contributions of GPVI to platelet biology, including its interaction with recently identified ligands such as fibrin and fibrinogen, and discusses therapeutic developments targeting GPVI to modulate platelet function and minimize bleeding outcomes.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Catherine Angenieux, Adele Couvidou, Nathalie Brouard, Anita Eckly, Arnaud Dupuls, Pierre H. Mangin, Blandine Maitre
Summary: This study assessed platelet reactivity based on HLA-I expression level, which allowed the identification of three platelet subpopulations according to their age. The results showed that the young HLA-Ihigh platelet population was the most reactive and prone to procoagulation. These findings provide new perspectives for investigating the role of young and old platelets.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2023)
Meeting Abstract
Hematology
Adele Couvidou, Catherine Angenieux, Laurie Ruch, Pierre Mangin, Christian Gachet, Blandine Maitre
