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 activation system and, presumably as a result thereof, generally has thrombo-resistant properties. The present investigation was undertaken to determine what density of immobilized heparin molecules expressing functionally intact antithrombin binding sites is required to achieve these blood 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 densities of antithrombin binding sites ranged from 1 to 28 pmol/cm2. The surfaces expressing 4 pmol/cm2 or more of specific antithrombin binding sites generated no measurable enzymatic activity in contact with plasma, either on the exposed surfaces or in the plasma phases. Below this level, the degree of activation gradually increased with decreasing densities, and in parallel the thrombo-resistant properties deteriorated. Addition of heparin to the plasma phase reduced the capacity of the heparin surfaces to bind antithrombin, leading to a diminished ability of the surfaces to prevent contact activation. This finding supports the hypothesis that antithrombin is the critical coagulation inhibitor for the suppression of contact activation on end-point immobilized heparin.
Sánchez
J
J
Department of Surgery, Karolinska Hospital, Stockholm, Sweden. jass@expk-ir.ks.se
Elgue
G
G
Riesenfeld
J
J
Olsson
P
P
D000925:Anticoagulants / Q000494:pharmacology; D000990:Antithrombin III; D001665:Binding Sites; D001672:Biocompatible Materials / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008422:Materials Testing; D010949:Plasma / Q000187:drug effects / Q000502:physiology*; D013499:Surface Properties; D013927:Thrombosis / Q000517:prevention & control*
D000925:Anticoagulants; D001672:Biocompatible Materials; D000990:Antithrombin III; D006493:Heparin