Article
Hematology
Gina Perrella, Jingnan Huang, Isabella Provenzale, Frauke Swieringa, Floor C. J. Heubel-Moenen, Richard W. Farndale, Mark Roest, Paola E. J. van der Meijden, Mark Thomas, Robert A. S. Ariens, Martine Jandrot-Perrus, Steve P. Watson, Johan W. M. Heemskerk
Summary: The study revealed that fibrin fibers play a consolidating role in microthrombus formation through nonredundant signaling of platelet glycoprotein VI and integrin alpha IIb beta 3 via Syk and low-level Ca2+ rises, even in the absence of thrombin, leading to minimal thrombin generation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Stefano Navarro, David Stegner, Bernhard Nieswandt, Johan W. M. Heemskerk, Marijke J. E. Kuijpers
Summary: This study utilized microfluidics technology and pharmacological intervention to acutely block and investigate key pathways of thrombus and clot formation in a short period of time, revealing the crucial roles of certain molecular pathways in the initial minutes of thrombus buildup.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
Article
Chemistry, Multidisciplinary
Aditya Girish, Ketan Jolly, Nijmeh Alsaadi, Maria de la Fuente, Arielle Recchione, Ran An, Dante Disharoon, Zachary Secunda, Shruti Raghunathan, Norman F. Luc, Cian Desai, Elizabeth Knauss, Xu Han, Keren Hu, Hanyang Wang, Ujjal Didar Singh Sekhon, Nathan Rohner, Umut A. Gurkan, Marvin Nieman, Matthew D. Neal, Anirban Sen Gupta
Summary: This study presents the design and evaluation of thrombin-loaded injury-site-targeted lipid nanoparticles (t-TLNPs) that can specifically localize at an injury site and release thrombin for hemostatic action. The nanoparticles were found to restore hemostatic dysfunction and reduce bleeding in both in vitro and in vivo experiments.
Article
Biochemistry & Molecular Biology
Ivan A. Muravlev, Anatoly B. Dobrovolsky, Olga A. Antonova, Svetlana G. Khaspekova, Amina K. Alieva, Dmitry V. Pevzner, Alexey V. Mazurov
Summary: Activated platelets play a role in blood coagulation by exposing phosphatidylserine (PS). Antiplatelet drugs have been found to have inhibitory effects on platelet impact in clot formation and PS exposure.
Review
Pharmacology & Pharmacy
Belay Tesfamariam, Steven C. Wood
Summary: Activated platelets protect circulating tumor cells from shear stress and promote their evasion from immune surveillance. They release transforming growth factor-81 (TGF-81) into the tumor microenvironment, inducing phenotypic changes that facilitate tumor cell dissemination and metastasis. Targeting the GPVI/FcR gamma-chain complex could potentially disrupt the platelet-tumor cell interaction without interfering with hemostasis.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Hematology
Rui-Gang Xu, Julia S. Gauer, Stephen R. Baker, Alexandre Slater, Eleyna M. Martin, Helen R. McPherson, Cedric Duval, Iain W. Manfield, Arkadiusz M. Bonna, Steve P. Watson, Robert A. S. Ariens
Summary: The study demonstrates that dimeric GPVI binds to fibrinogen with higher affinity compared to the monomer, primarily through avidity effects. The interaction of GPVI with the α C-region of fibrinogen is crucial for its binding. These findings suggest that clustering of GPVI through the α C-region during fibrin polymerization may lead to downstream signaling, platelet activation, and clot growth.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Hematology
Gina Perrella, Magdolna Nagy, Steve P. Watson, Johan W. M. Heemskerk
Summary: GPVI is a receptor expressed on megakaryocytes and platelets that plays a role in both arterial and venous thrombus formation, as well as in the formation of platelet-leukocyte complexes. It is emerging as a potential therapeutic target for venous thrombosis, pulmonary thromboembolism, and cancer metastasis due to its involvement in venous thrombus formation and thromboinflammation. Circulating soluble GPVI is also being explored as a biomarker for thrombosis-related complications.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Hematology
Claudia Khayat, Rita Marchi, Stephane Durual, Thomas Lecompte, Marguerite Neerman-Arbez, Alessandro Casini
Summary: This study investigated the impact of fibrinogen concentrate (FC) infusion on thrombin generation parameters and fibrin clot structure in patients with inherited afibrinogenemia. The results showed that FC infusion increased thrombin potential and peaks, but lag times and thrombin peaks were still lower than healthy controls. Fibrin clot structure formed after FC infusion was similar to patients with hypofibrinogenemia. These findings suggest that FC may not induce hypercoagulability in patients with afibrinogenemia.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Multidisciplinary Sciences
Isuru Induruwa, Harriet McKinney, Carly Kempster, Patrick Thomas, Joana Batista, Jean-Daniel Malcor, Arkadiusz Bonna, Joanne McGee, Elaine Bumanlag-Amis, Karola Rehnstrom, Sophie Ashford, Kenji Soejima, Willem Ouwehand, Richard Farndale, Kate Downes, Elizabeth Warburton, Masaaki Moroi, Stephanie Jung
Summary: Patients with stroke express more GPVI-dimer on their platelet surface at presentation, lasting at least until day-90 post-stroke. This finding provides evidence for anti-thrombotic targeting of GPVI-dimer in ischemic stroke.
Article
Hematology
Julia S. Gauer, Cedric Duval, Rui-Gang Xu, Fraser L. Macrae, Helen R. McPherson, Christian Tiede, Darren Tomlinson, Steve P. Watson, Robert A. S. Ariens
Summary: The interaction between GPVI and fibrin significantly affects the formation of procoagulant platelets and the structure of blood clots. Inhibition of GPVI signaling increases clot porosity and impairs clot contractibility to varying degrees.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Tanvi Rudran, Silvio Antoniak, Matthew J. Flick, Mark H. Ginsberg, Alisa S. Wolberg, Wolfgang Bergmeier, Robert H. Lee
Summary: This study investigated the specific receptors and signaling pathways required for platelet function in thromboelastography (TEG) using genetic and pharmacologic inhibition of platelet proteins in mouse and human blood samples. The results showed that standard TEG is not sensitive to platelet signaling pathways critical for integrin inside-out activation and platelet hemostatic function. Furthermore, this study provides the first evidence that PARs and glycoprotein VI play redundant roles in platelet-mediated clot contraction in TEG.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Veterinary Sciences
Anamika Changrani-Rastogi, Krutika Swadi, Mitali Barve, Niyati Bajekal
Summary: This study evaluated the effect of autologous platelet-rich fibrin (PRF) in the management of feline cutaneous wounds. The results showed that PRF could serve as a low-risk and convenient adjunctive therapy to promote wound healing in cats.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Hematology
Vijay K. Sonkar, Alicia S. Eustes, Azaj Ahmed, Melissa Jensen, Mitali V. Solanki, Jagadish Swamy, Rahul Kumar, Trevor P. Fidler, Jon C. D. Houtman, Bryan G. Allen, Douglas R. Spitz, E. Dale Abel, Sanjana Dayal
Summary: Reactive oxygen species (ROS) contribute to platelet hyperactivation during aging. In this study, it was found that mitochondria are an important source of platelet ROS and that mitochondrial SOD2 protects against mitochondrial ROS-driven platelet activation and thrombosis during aging.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Cell Biology
Aleksander Siniarski, Aleksandra Gasecka, Milosz Starczynski, Marta Banaszkiewicz, Szymon Darocha, Adam Torbicki, Marcin Kurzyna, Krzysztof J. Filipiak, Jadwiga Nessler, Grzegorz Gajos
Summary: This study compared platelet reactivity, thrombin generation, clot permeation, and lysis properties in PAH patients receiving PGI2 analogues and those not receiving them. The results showed that patients treated with PGI2 analogues had reduced platelet reactivity compared to the control group, but there were no differences in clot formation and lysis parameters.
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.
Article
Hematology
Jean-Philippe Desilles, Mialitiana Solo Nomenjanahary, Arturo Consoli, Veronique Ollivier, Dorothee Faille, Marie-Charlotte Bourrienne, Mylene Hamdani, Sebastien Dupont, Lucas Di Meglio, Simon Escalard, Benjamin Maier, Raphael Blanc, Michel Piotin, Bertrand Lapergue, Nadine Ajzenberg, Marc Vasse, Mikael Mazighi, Benoit Ho-Tin-Noe
Summary: The study reveals that COVID-19 does not affect the content of NETs or worsens the fibrinolysis resistance of AIS thrombi. The therapeutic hurdle can be overcome by DNase 1, even in the context of SARS-CoV-2 infection.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
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
Hematology
Quentin Kimmerlin, Sylvie Moog, Alexandra Yakusheva, Catherine Ziessel, Anita Eckly, Monique Freund, Gabor Zavodszky, Yannick Knapp, Pierre Mangin, Francois Lanza
Summary: The discoid morphology of blood platelets is crucial for hemostasis. This study generated a mouse model lacking specific tubulin isoforms and found that the absence of these isoforms resulted in severe bleeding disorder and impaired platelet adhesion and aggregation. These findings highlight the importance of platelet morphology.
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)
Editorial Material
Hematology
James D. McFadyen, Pierre H. Mangin, Karlheinz Peter
THROMBOSIS AND HAEMOSTASIS
(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)
