IN-VITRO CONTACT PHASE ACTIVATION WITH HEMODIALYSIS MEMBRANES - ROLE OF PHARMACEUTICAL AGENTS

Contact phase activation was investigated in vitro using flat sheet ty pe of haemodialysis membranes, Cuprophan (Akzo, Faser, Germany) and AN 69S (Hospal, France), and a negatively charged polyamide Ultipor NR 14 225 membrane as a control. The investigation focussed on the determina tion of factor XII-like activity (FXIIA) as an indicator of contact ph ase activation in the supernatant phase and at the membrane surface af ter plasma-membrane contact using an incubation test cell. The finding s were compared with the observations from a plasma-free system utiliz ing purified unactivated factor XII. The plasma FXIIA bound to the mem brane surface was significantly different between the membranes, while the supernatant phase FXIIA exhibited no significant differences. In contrast, the plasma-free system exhibited significant differences in the supernatant FXIIA and membrane-bound FXIIA for all the materials u sed and the magnitude of the activity was significantly greater for ne gatively charged materials. This finding demonstrated the strong influ ence of the interaction of other plasma constituents on the membrane s urface and as such the binding and subsequent activation of factor XII may be altered possibly due to competitive binding and steric hindran ce. On the addition of anticoagulants such as heparin, low-molecular-w eigh heparin, citrate and hirudin, no significant differences were obs erved in plasma supernatant phase FXIIA. However, each anticoagulant a ppears to have a distinct influence on the magnitude of plasma membran e-bound FXIIA. On the addition of aprotinin (a kallikrein inhibitor), no significant differences were observed in the plasma supernatant FXI IA. In contrast, aprotinin appears to significantly reduce membrane-bo und FXIIA on Cuprophan and polyamide NR, but significantly increase th e magnitude of the membrane-bound FXIIA on AN69S.