Boffa M C, Labarre D, Jozefowicz M, Boffa G A
Thromb Haemost. 1979 Apr 23;41(2):346-56.
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.
通过在肝素存在下由Ce4+离子引发的氧化反应，使甲基丙烯酸甲酯进行自由基聚合，合成了一种固态肝素 - 聚甲基丙烯酸甲酯共聚物。共价连接的肝素占共聚物重量的10%。该共聚物的抗凝血酶活性相当于接枝肝素的1%。共聚物的聚甲基丙烯酸甲酯序列在纤维蛋白原、免疫球蛋白、转铁蛋白和白蛋白吸附中起主导作用。这些吸附在共聚物上的蛋白质在全血浆存在下表现出不同的竞争性解吸模式：纤维蛋白原对共聚物的亲和力最高。共聚物的肝素部分负责抗凝血酶III的吸附以及因子V活性的降低。活性抗凝血酶III被洗脱。使用高浓度的可溶性肝素时，观察到血浆中因子V的失活。该结果表明，即使共聚物的肝素链缺乏抗凝血酶活性，也参与了这种失活过程。对于肝素 - 聚甲基丙烯酸甲酯共聚物，血浆凝血酶原的行为与在肝素 - 琼脂糖共聚物上不同：观察到因子XI活性消失、前激肽释放酶活性降低以及因子IX激活。聚甲基丙烯酸甲酯序列负责因子IX的激活。
