CONTROL OF CONTACT ACTIVATION ON END-POINT IMMOBILIZED HEPARIN - THE ROLE OF ANTITHROMBIN AND THE SPECIFIC ANTITHROMBIN-BINDING SEQUENCE

The uptake and activation of FXII from blood plasma was studied in sma ll-diameter polyethylene tubing, surface-modified by end-point immobil ization of heparin. Two preparations of heparin were used to modify th e contact-activating properties of the plastic tubing: unfractionated, functionally active heparin and low-affinity heparin, lacking the spe cific antithrombin-binding sequence and virtually devoid of anticoagul ant activity. The uptakes of FXII on the two heparin surfaces were sim ilar. No activated FXII could be demonstrated on the unfractionated he parin surface, whereas on the low-affinity heparin surface nearly all FXII underwent spontaneous activation. The suppression of FXII activat ion on the unfractionated heparin surface was investigated by using pl asma depleted of antithrombin, complement C1 esterase inhibitor, or bo th. The removal of antithrombin resulted in extensive activation of FX II, whereas the depletion of C1 esterase inhibitor had only a minor ef fect. Experiments with recalcified plasma showed rapid clot formation during exposure to the low-affinity heparin surface. After depletion o f antithrombin, but not complement C1 esterase inhibitor, the recalcif ied plasma clotted in contact with the unfractionated heparin surface as well. We conclude that antithrombin and the antithrombin-binding se quence in the surface-immobilized heparin are essential for the preven tion of surface activation of FXII and triggering of the intrinsic coa gulation system. (C) 1995 John Wiley and Sons, Inc.