Phosphorylated polystyrene derivatives with different compositions in phosphate groups were shown to be either recognized as phospholipidic or as DNA-like surfaces by antibodies from Systemic Lupus Erythematosus patients. In order to check whether these polymers were able to interact with Vitamin K-dependent coagulation factors, phosphorylated resins of various compositions in phosphate groups were assessed with regard to their interactions with Factor II, one of the Vitamin K-dependent factors. These studies were performed either in the presence or the absence of calcium ions, and with or without albumin precoating of the polymers. The results show that the affinity of the protein for the polymer is increased in the presence of calcium ions and depends on the composition of the polymer. The protein-polymer interactions involve the formation of binary or ternary complexes and the domains of predominance of these complexes were determined as a function of the calcium ion concentration in the assay. This allowed us to propose optimal conditions for Factor II purification by highly specific liquid chromatography using phosphorylated polystyrene resins of given compositions as stationary phases.