Thrombosis can cause the occlusion of implantable medical devices, leading to the rejection of the device and subsequent mortality. Thrombosis is primarily induced by red blood aggregation and coagulation. The administration of anticoagulant drugs is generally used as a treatment to avoid these processes. Adverse effects such as bleeding in the event of an anticoagulant overdose, osteoporosis associated with prolonged use, hypersensitivity, and hives have been reported. New strategies such as biomolecule surface functionalization have recently been studied to overcome these problems. In this study, we report a novel coating composed of polydopamine (PDA) and proanthocyanidins (PACs) from blueberry extract to avoid red blood aggregation in short-term use medical devices such as silicone catheters. We showed that PDA formed stable films on silicone surfaces and PACs could be immobilized on PDA layers using laccase as a catalyst. The PDA–PACs films decreased surface hydrophilicity, increased surface roughness, and decreased plasma protein adsorption. The films were stable in phosphate buffer saline (PBS) and cell culture media. Furthermore, red blood cell adsorption and aggregation decreased. These effects are attributed to changes in the membrane fluidity that influences adhesion, the steric hindrance of the layers, and the low adsorption of plasma proteins on the PAC layer.