INHIBITION OF THE PLASMA CONTACT ACTIVATION SYSTEM OF IMMOBILIZED HEPARIN - RELATION TO SURFACE-DENSITY OF FUNCTIONAL ANTITHROMBIN BINDING-SITES

End-point immobilization of heparin to artificial materials gives rise to a surface that prevents triggering of the plasma contact activatio n system and, presumably as a result thereof, generally has thrombo-re sistant properties. The present investigation was undertaken to determ ine what density of immobilized heparin molecules expressing functiona lly intact antithrombin binding sites is required to achieve these blo od compatible properties. Six different heparin surfaces were prepared on polyethylene tubing and studied in contact with human plasma. The content of bound heparin was the same on all surfaces while the densit ies of antithrombin binding sites ranged from 1 to 28 pmol/cm(2). The surfaces expressing 4 pmol/cm(2) or more of specific antithrombin bind ing sites generated no measurable enzymatic activity in contact with p lasma, either on the exposed surfaces or in the plasma phases. Below t his level, the degree of activation gradually increased with decreasin g densities, and in parallel the thrombo-resistant properties deterior ated. Addition of heparin to the plasma phase reduced the capacity of the heparin surfaces to bind antithrombin, leading to a diminished abi lity of the surfaces to prevent contact activation. This finding suppo rts the hypothesis that antithrombin is the critical coagulation inhib itor for the suppression of contact activation on end-point immobilize d heparin. (C) 1997 John Wiley & Sons, Inc.