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Exosite crosstalk in thrombin.
J Thromb Haemost
January 2025
Department of Medicine, McMaster University; Department of Biochemistry and Biomedical Sciences, McMaster University; Thrombosis and Atherosclerosis Research Institute, McMaster University and Hamilton Health Sciences.
Thrombin is the central mediator of hemostasis, where it converts fibrinogen to fibrin, activates upstream factors to promote coagulation, activates factor XIII and thrombin-activatable fibrinolysis inhibitor to stabilize fibrin, mediates anticoagulation, and modulates cellular activity via cell surface receptors. Thus, regulation of thrombin activity is essential to the hemostatic balance. Thrombin is regulated by positively charged surface domains that surround the active site.
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Blood
January 2025
KULeuven, Leuven, Belgium.
Thrombomodulin (TM) expressed on endothelial cells regulates coagulation. Specific nonsense variants in the TM gene, THBD, result in high soluble TM levels causing rare bleeding disorder. In contrast, though THBD variants have been associated with venous thromboembolism, this association remains controversial.
View Article and Find Full Text PDFArtificial biomarker-based feedback-regulated personalized and precise thrombolysis with lower hemorrhagic risk.
Sci Adv
January 2025
Department of Cell Biology, Third Military Medical University, Chongqing, China.
The body weight-based thrombolytic medication strategy in clinical trials shows critical defects in recanalization rate and post-thrombolysis hemorrhage. Methods for perceiving thrombi heterogeneity of thrombolysis resistance is urgently needed for precise thrombolysis. Here, we revealed the relationship between the thrombin heterogeneity and the thrombolysis resistance in thrombi and created an artificial biomarker-based nano-patrol system with robotic functional logic to perceive and report the thrombolysis resistance of thrombi.
View Article and Find Full Text PDFReal-Time Imaging of Platelet-Initiated Plasma Clot Formation and Lysis Unveils Distinct Impacts of Anticoagulants.
Thromb Haemost
January 2025
Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Background: Fibrinolysis is spatiotemporally well-regulated and greatly influenced by activated platelets and coagulation activity. Our previous real-time imaging analyses revealed that clotting commences on activated platelet surfaces, resulting in uneven-density fibrin structures, and that fibrinolysis initiates in dense fibrin regions and extends to the periphery. Despite the widespread clinical use of direct oral anticoagulants (DOACs), their impact on thrombin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrinolysis remains unclear.
View Article and Find Full Text PDFTRAP-Induced Platelet Reactivity Is Inhibited by Omega-3 Fatty Acid-Derived Prostaglandin E3 (PGE3).
Biomedicines
December 2024
Department of Physiology, University of Murcia, 30120 Murcia, Spain.
Prostaglandins are naturally occurring local mediators that can participate in the modulation of the cardiovascular system through their interaction with Gs/Gi-coupled receptors in different tissues and cells, including platelets. Thrombin is one of the most important factors that regulates platelet reactivity and coagulation. Clinical trials have consistently shown that omega-3 fatty acid supplementation lowers the risk for cardiovascular mortality and morbidity.
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