Direct thrombin inhibiting coating for active coagulant management in extracorporeal circulation

Abstract

Existing anticoagulant coatings are designed to inhibit the initial attachment of coagulant factors, but they frequently suffer from undesirable coating defects that result in a declined physical barrier function. Heparin, serving as a commercialized pharmacological coating via the activation of antithrombin, frequently causes heparin-induced thrombocytopenia. Here, we developed an argatroban-polyphenol conjugate proteinaceous coating (named PDA-BSA-AG coating) that actively inhibits thrombin, in contrast to previously reported passive coatings and indirect pharmacological anticoagulants. Following clinical treatment standards, a magnetic levitation ventricular assist system was employed for the first time to accomplish extracorporeal circulation utilizing PDA-BSA-AG coated tubes. The results show that the clotting time of the PDA-BSA-AG coating was 68.9 % longer than that of clinical Bioline heparin coating. It is noteworthy that argatroban not only delivers anticoagulant effectiveness but also enhances patient safety and reduces the occurrence of complications. A novel combination of the primary specific proteins of platelets and the coagulation-inflammatory cascade reaction of the cytokines and complement systems explained the anticoagulation mechanism. Reliable biocompatibility (hemolysis, cytotoxicity, and antibacterial activity) was noted, along with impressive coating stability for up to 6 h of extracorporeal circulation. These results above suggested that the PDA-BSA-AG coating is promising for a wide range of blood-contacting devices.