Preparation and blood compatibility of polyethersulfone dialysis membrane modified by apixaban as coagulation factor Xa inhibitor.

Abstract

Blood purification therapy is widely used in the treatment of critically ill patients. However, most dialysis membranes are prone to thrombosis. Activated coagulation factor X (FXa) functions at the intersection of intrinsic, extrinsic, and common coagulation pathways and plays a central role in thrombogenesis. To date, few dialysis membranes that directly inhibit FXa have been reported. We modified a polyethersulfone(PES) membrane using apixaban as an FXa inhibitor and investigated the performance of this membrane (AMPES). The contact angle of the modified membrane was reduced. PWF and retention rates of BSA were increased, demonstrating good hydrophilicity and dialysis performance. Albumin adsorption was reduced from 141.8±15.5 to 114.1±6.9μgcm-2. Reduced protein adsorption, especially targeted anti-FXa effect, inhibited the activation of intrinsic, extrinsic, and common coagulation pathways, as evidenced by significant prolongations of activated partial thromboplastin time, prothrombin time, and thrombin time by 145.04, 46.84 and 11.46s, respectively. Furthermore, we determined the FXa concentration of each group, and found that the modified membrane had better anticoagulant performance through the inhibition of FXa. Favorable antiplatelet activity was also demonstrated. Thromboelastogram was used to comprehensively evaluate the anticoagulant and antithrombotic activities of the modified membrane. The R value was increased by 43.1min, while the reduction in α angle was 42.5°. The coagulation comprehensive index reduction was 34.3. In addition, C3a and C5a were decreased by 15.3% and 30.4%, respectively. Furthermore, in vitro cytotoxicity and erythrocyte stability testing as well as in vivo murine experiments demonstrated the biosafety of the modified membrane. These results indicate that the AMPES dialysis membrane has an excellent potential for clinical applications.