Anticoagulation treatment for patients with high bleeding risk during hemodialysis is challenging. Contact between the dialysis membrane and the blood leads to protein adsorption and activation of the coagulation cascade reaction. Activated coagulation Factor X (FXa) plays a central role in thrombogenesis, but anticoagulant modification of the dialysis membrane is rarely targeted at FXa. In this study, we constructed an anticoagulant membrane using the polydopamine coating method to graft FXa inhibitors (apixaban and rivaroxaban) on the membrane surface. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used to characterize the membranes. The apixaban- and rivaroxabanmodified membranes showed lower water contact angles, decreased albumin protein adsorption, and suppressed platelet adhesion and activation compared to the unmodified PES membranes. Moreover, the modified membranes prolonged the blood clotting times in both the intrinsic and extrinsic coagulation pathways and inhibited FXa generation and complement activation, which suggested that the modified membrane enhanced biocompatibility and antithrombotic properties through the inhibition of FXa. Targeting FXa to design antithrombotic HD membranes or other blood contact materials might have great application potential.
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http://dx.doi.org/10.1080/09205063.2024.2384275 | DOI Listing |
Thromb Res
January 2025
Neurology and Stroke Unit, AORN "Antonio Cardarelli", Naples, Italy. Electronic address:
Res Pract Thromb Haemost
November 2024
Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.
Background: Anticoagulants prevent the formation of potentially fatal blood clots. Apixaban is a direct oral anticoagulant that inhibits factor (F)Xa, thereby impeding the conversion of prothrombin into thrombin and the formation of blood clots. Blood clots are held together by fibrin networks that must be broken down (fibrinolysis) to restore blood flow.
View Article and Find Full Text PDFJ Thromb Haemost
November 2024
Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University, Solna, Sweden.
Background: In the splice variant factor (F)V-Short, 702 residues are deleted from the B domain, resulting in exposure of an acid region (AR2; 1493-1537) that binds TFPIα. FV-Short and protein S serve as synergistic TFPIα cofactors in inhibition of FXa. In the preAR2 region, a hydrophobic patch PLVIVGL (1481-1487) is crucial for synergistic TFPIα-cofactor activity and assembly of FV-Short, TFPIα, and protein S.
View Article and Find Full Text PDFJ Thromb Haemost
November 2024
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands. Electronic address:
Pharmaceuticals (Basel)
October 2024
Sysmex Corporation, Kobe 651-2241, Japan.
The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF.
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