Incorporation of Danaparoid to enhance anticoagulant activity of hollow fiber membranes

Hemodialysis is a life-saving treatment for patients with End Stage Kidney Disease. However, the interaction of blood with the membranes can lead to protein adsorption, platelet activation and blood cell deposition that reduce the available surface area of dialysis membranes, hindering dialysis performance, and can lead to the formation of blood clots and thromboembolism in patients. For this reason, better membranes with improved hemocompatibility are needed. In this study, we incorporate Danaparoid and Heparin into hollow fiber membranes to improve their local anticoagulant activity. Danaparoid has recently been reported to have better hemocompatibility compared to Heparin in in vitro blood studies, making it a promising candidate for membrane biofunctionalization. We investigated its incorporation into membranes via blending into the polymer solution during membrane fabrication, and via post-fabrication coating of in-house and commercially available dialysis membranes (Nipro Elisio 19 HX and Fresenius FX1000). Coating of membranes localizes Danaparoid at the inner membrane surface and leads to higher and more reproducible anti-factor Xa activity compared to blending. Danaparoid also remained localized at the membrane surface, with no indication of release into the recirculated plasma after 2 hours. Moreover, during transport studies, membranes coated with Danaparoid showed a slower increase in blood pressure than unmodified membranes, indicating reduced formation of fouling and blood cell deposition in the lumen of the fibers, while maintaining creatinine removal comparable to commercial FX1000 membranes.