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A cell-based model to study mechanisms of endothelial-dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine.
Res Pract Thromb Haemost
January 2025
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Background: Inflammation is a driver of thrombosis, but the phenomenon of thromboinflammation has been defined only recently, bringing together the multiple pathways involved. models can support the development of new therapeutics targeting the endothelium and also assess the existing immunomodulatory drugs, such as hydroxychloroquine, in modulating the inflammation-driven endothelial prothrombotic phenotype.
Objectives: To develop a model for thrombin generation (TG) on the surface of human endothelial cells (ECs) to assess pro/antithrombotic properties in response to inflammation.
Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.
Bioconjug Chem
January 2025
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-5127, United States.
Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119.
View Article and Find Full Text PDFProtection of β2GPI-Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation.
Blood
January 2025
Cleveland Clinic, Cleveland, Ohio, United States.
Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI.
View Article and Find Full Text PDFExtracellular vesicles in ageing cold-stored whole blood may not compensate for the decreasing haemostatic function in vitro.
Transfus Med
January 2025
Research and Development, Finnish Red Cross Blood Service, Vantaa, Finland.
Background: Extracellular vesicles (EVs) have procoagulative properties. As EVs are known to accumulate in stored blood products, we compared the EV content and coagulation capacity of leukoreduced cold-stored whole blood (CSWB) with current prehospital and in-hospital component therapies to understand the role of EVs in the haemostatic capacity of ageing CSWB.
Materials And Methods: Blood was obtained from 12 O RhD-positive male donors.
No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy.
Res Pract Thromb Haemost
January 2025
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Background: Emicizumab, a bispecific antibody that mimics factor (F)VIII, has significantly improved hemophilia A management. Although emicizumab levels can be measured, tools for estimating the hemostatic efficacy of emicizumab are lacking. Thrombin generation (TG) assays can distinguish bleeding phenotypes in persons with hemophilia A on FVIII prophylaxis and may also be used during emicizumab therapy.
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