Plasma Contact Activation and Decrease of Factor V Activity on Negatively-Charged Polyelectrolytes

Summary

The effect of negatively-charged polymers, used in some artificial devices, on plasma clotting and kinin systems was studied in vitro using polyelectrolyte complexes.

Contact activation was observed as an immediate, transient and surface-dependent phenomenon. After incubation of the plasma with the polymer a small decrease of factor XII activity was noticed, which corresponded to a greater reduction of prekallikrein activity and to a marked kinin release. No significant decrease of factor XII, prekallikrein, HMW kininogen could be detected immunologically. Only the initial contact of the plasma with the polyelectrolyte lead to activation, subsequently the surface became inert.

Beside contact activation, factor V activity also decreased in the plasma. The decrease was surface and time-dependent. It was independent of contact factor activation, and appeared to be related to the sulfonated groups of the polymer. If purified factor V was used instead of plasma factor V, inactivation was immediate and not time-dependent suggesting a direct adsorption on the surface. A second incubation of the plasma-contacted polymer with fresh plasma resulted in a further loss of Factor V activity.

Key Words

Negatively-charged polymers - Polyelectrolyte complex - Contact factors - Factor V

• References

• 1 Vogel MK, Cross RA, Bixler HJ, Guzman RJ. Medical uses for polyelectrolytes complexes. J Macromol Sci Chem 1970; 3: 675-693
• 2 Nelsen L, Cross RA, Vogel MA, Gott VL, Fadali AM. Synthetic thromboresistant surfaces from sulfonated polyelectrolyte complexes. Surgery 1970; 67: 826-830
• 3 Nossel HL, Wilner GD, Leroy EC. Importance of polar groups for initiating blood coagulation and aggregating platelets. Nature 1969; 221: 75-76
• 4 Boffa MC, Farges JP, Dreyer B, Conche B, Pusineri C, Vantard G. Striking differences observed in the effect of amphipathic polyelectrolytes on contact and other clotting factors. In: Biomaterials. Winter GD, Gibbons DF, Plenck H. (eds) New York: 1980. pp 399-408
• 5 Pusineri C, Sedivy P, Carruette A, Granger A, Sausse A. Some approaches to blood-compatible materials. In: Physiological and Clinical Aspects of Oxygenator Design. David SG, Engell HC. (eds) Elsevier, Amsterdam, Oxford; New York: 1976. pp 303-318
• 6 Adamson AW. The BET and related isotherms in Physical chemistry of surfaces. John Wiley & Son; New York: 1976. pp 565-571
• 7 Dahlbäck B. Human coagulation factor V purification and thrombin- catalyzed activation. J Clin Invest 1980; 66: 583-591
• 8 Horowitz MS. Harpel method for partial purification of human plasma prekallikrein. Proceedings of the work-shop on the measurement of potentially hypotensive agents Bureau of Biologies Food and Drug Administration, Bethesda. Maryland: 1977. pp 15-16
• 9 Soulier JP, Gozin D. Assay of Fletcher factor (plasma prekallikrein) using an artificial clotting reagent and a modified chromogenic assay. Thromb Haemostas 1979; 42: 538-547
• 10 Cochrane CG, Griffin JH. Molecular assembly in the contact phase of the Hageman factor system. Am J Med 1979; 67: 657-664
• 11 Cochrane CG, Revak SD. Dissemination of contact activation in plasma by plasma prekallikrein. J Exp Med 1980; 152: 608-619
• 12 Revak SD, Cochrane CG, Griffin JH. The binding and cleavage characteristics of human Hageman factor dining contact activation. J Clin Invest 1977; 59: 1167-1175
• 13 Wiggings RC, Bouma BN, Cochrane CG, Griffin JH. Role of high molecular weight kininogen in surface-binding and activation of coagulation factor XI and prekallikrein. Proc Natl Acad Sd, USA 1977; 74: 4636-4660
• 14 Silverberg M, Nicoll JE, Kaplan AP. The mechanism by which the light chain of cleaved HMW-kininogen augments the activation of prekallikrein, factor XI and Hageman factor. Thromb Res 1980; 20: 173-189
• 15 Kerberiou DM, Griffin JH. Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma J Biol Chem 1979; 254: 12020-12027
• 16 Schiffman S, Mannhalter C, Tyner KD. Human high molecular weight kininogen. Effects of cleavage by kallikrein on protein structure and procoagulant activity J Biol Chem 1980; 255: 6433-6438
• 17 Margolis J. The mode of action of Hageman factor in the release of plasma kinin. J Physiol 1960; 151: 328
• 18 Boffa MC, Labarre D, Jozefowicz M, Boffa GA. Interactions between human plasma proteins and heparin-poly(methyl-methacry-late) copolymer. Thromb Res 1979; 41: 346-355
• 19 Sultan Y, Maisonneuve P, Pusineri C. Characterization of artificial surfaces by protein adsorption and platelet adherence. Abstracts -1st World Biomaterial Congress; Baden: 1980. pp 2.5.4