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The thrombosis of the extracorporeal circuits leads to serious complications, which affect the life safety of the patients significantly. However, intravenous anticoagulants such as heparin may induce bleeding, hypersensitivity, and other adverse reactions. In this study, the mussel-inspired composite coating consisting of polydopamine (PDAM), lysine, and modified heparin was constructed on the commonly used medical poly(vinyl chloride) (PVC) tubes to reduce thrombosis by combining the immobilization of anticoagulants and the construction of bioinert surface strategies. First, the PDAM/lysine coating rich in amine groups was constructed in a mixed solution of dopamine and lysine through the co-deposition reaction. Then, the modified heparin was covalently immobilized on the PDAM/lysine coating to obtain composite coating. Finally, the graft density and stability of heparin and anticoagulant properties of the composite coating were tested. The results showed that the composite coating could inhibit the adhesion and activation of platelets significantly and prolong the activated partial thromboplastin time (APTT) remarkably for over 25 s. The composite coating also had excellent hemocompatibility, and the hemolysis ratio was less than 0.5%. Particularly, the anticoagulant coating performed well in the in vitro blood circulation test. The composite coating constructed in this work show great potential in the anticoagulant treatment for medical devices.