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

Summary

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.

• References

• 1 Boffa MC, Delori P, Soulier JP. 1972; Anticoagulant factors from viperidae venoms. Platelets phospholipid inhibitors Thrombosis et Diathesis Haemorrhagica 28: 509
• 2 Boffa GA, Lucien N, Faure A, Boffa MC, Jozefonvicz J, Szubarga A, Mandon P, Larrieu MJ. 1977; Polytetrafluoroethylene-N-vinylpyrrolidone graft copolymers: affinity with plasma proteins. Journal of Biomedical Materials Research 11: 317
• 3 Cifonelli JA. 1974; The relationship of molecular weight, and sulfate content and distribution to anticoagulant activity of heparin preparations. Carbohydrate 37: 145
• 4 Colman RW, Bagdasarian A. 1976. Human kalhkrein and prekallikrein. In: Lorand L. (Ed.) Methods in Enzymology. New York - San Francisco - London: Academic Press; XLV 313
• 5 Danishefsky I, Ahrens M, Klein S. 1977; Effects of heparin modifications on its activity in enhancing the inhibition of thrombin by antithrombin III. Biochimica et Biophysica Acta 498: 215
• 6 Danishefsky I, Tzeng F. 1974; Preparation of heparin linked agarose and its interaction with plasma. Thrombosis Research 4: 237
• 7 Danishefsky I, Tzeng F, Ahrens M, Klein S. 1976; Synthesis of heparin sepharoses and their binding with thrombin and antithrombin-heparin cofactor. Thrombosis Research 8: 131
• 8 Fujikawa K, Davie EW. 1976. Bovine factor IX (Christmas Factor). In: LORAND L. (Ed.) Methods in Enzymology. New York - San Francisco - London: Academic Press; XLV 74
• 9 Fujikawa K, Walsh KA, Davie EW. 1977; Isolation and characterization of bovine factor XII (Hageman Factor). Biochemistry 16: 2270
• 10 Gentry PW, Alexander B. 1973; Specific coagulation factor adsorption to insoluble heparin. Biochemical and Biophysical Research Communications 50: 500
• 11 Habal FM, Movat HZ. 1976; Kininogens of human plasma. Seminars in Thrombosis and Haemostasis 3: 27
• 12 Holemans R, Vermylen C, Verstraete M. 1960; Disappearance of factor V activity after incubation of plasma with heparin and heparinoids. Thrombosis et Diathesis Haemorrhagica 4: 303
• 13 Koide T, Kato H, Davie EW. 1977; Isolation and characterization of bovine factor XI (Plasma thromboplastin antecedent). Biochemistry 16: 2279
• 14 Kurata M, Iwama M, Kamada K. 1966. Viscosity-molecular weight relationship. In: Brandrup J, Immergut EH. (Eds.) Polymer Handbook. New York: Interscience, Part IV p 25
• 15 Labarre D, Boffa MC, Jozefowicz M. 1974; Preparation and properties of Heparin-Poly (Methyl Methacrylate) copolymers. Journal of Polymer Science, Symposium n° 47: 131
• 16 Labarre D, Boffa MC, Jozefowicz M. 1977; Properties of Heparin Poly(Methyl Methacrylate) copolymers II. Journal of Biomedical Materials Research 11: 283
• 17 Lasker SE, Sttvala SS. 1966; Physico chemical studies of fractionated bovine heparin. I. Some diluted solution properties Archives of Biochemistry and Biophysics 115: 360
• 18 Marchalonis JJ. 1969; An enzyme method for the trace iodination of immunoglobulins and other proteins. Biochemical Journal 113: 299
• 19 Philip G, Moran J, Colman RW. 1970; Dissociation and association of the oligomeric forms of factor V. Biochemistry 9: 2212
• 20 Rosenberg RD. 1976. The function of heparin. In: Kakkar VV, Thomas DP. (Eds.) Heparin, Chemistry and Clinical Usage. London - New York - San Francisco: Academic Press; 101
• 21 Soulier JP, Larrieu MJ. 1952; Etude analytique des temps de Quick allongés. Dosages de prothrombine, de proconvertine et de proaccélérine. Sang 23: 549
• 22 Soulier JP, Larrieu MJ. 1953; Nouvelle methode de diagnostic de l’hemophilie. Dosage des facteurs antihemophiliques A et B Sang 24: 205
• 23 Thompson RE, Mandle jr RJ, Kaplan AP. 1977; Interaction of factor XI and kallikrein with high molecular weight kininogen. Vlth International Congress on Thrombosis and Haemostasis, XHth Congress of the World Federation of Hemophilia Thrombosis and Haemostasis 31: 13
• 24 Vroman L. 1963; Effects of hydrophobic surfaces upon blood coagulation. Thrombosis et Diathesis Haemorrhagica 10: 455