Interactions between Human Plasma Proteins and Heparin-Poly(Methyl Methacrylate) Copolymer

Abstract

A solid Heparin-PMMA copolymer has been synthetized by a radical polymerization of methyl methacrylate from oxidative reaction initiated by Ce⁴⁺ ions in the presence of heparin. Covalently linked heparin was 10% of copolymer weight. The antithrombin activity of the copolymer corresponded to 1% of grafted heparin. PMMA sequence of the copolymer played the leading role in fibrinogen, immunoglobulins, transferrin and albumin adsorption. These proteins adsorbed on the copolymer, showed different competitive desorption pattern in the presence of whole plasma: fibrinogen presented the highest degree of affinity for the copolymer. The heparin part of the copolymer was responsible for antithrombin III adsorption and for decrease of factor V activity. Active antithrombin III was eluted. An inactivation of factor V in plasma was observed using high concentrations of soluble heparin. This result suggested that copolymer heparin chains, even devoid of antithrombin activity, were involved in this inactivation. With Heparin-PMMA copolymer, plasma clotting pro-enzymes behaved differently than on heparin-sepharose copolymer: disappearance of factor XI activity, decrease in prekallikrein activity and activation of factor IX were observed. PMMA sequences were responsible for factor IX activation.