PLASMA-ARTIFICIAL SURFACE INTERACTIONS; ROLE OF CONTACT AND FIBRINOLYTIC SYSTEMS

The transient adsorption of fibrinogen (Fg) to artificial surfaces (Vroman Effect) is modulated principally by the procofactor, high molecular weight kininogen (HK). We investigated which form of HK was responsible for Fg displacement and also whether other proteins participated in the Vroman Effect. Experiments were performed at 23°C with a 5 min surface exposure to various concentrations of either normal plasma or plasma deficient in specific proteins to which 125I Fg had been added. Typically, Fg adsorption reached a maximum at 1% plasma and decreased at higher plasma concentrations. On all surfaces tested, Fg displacement was greatly reduced in HK-deficient plasma. Normal plasma,when exposed to the contact system activator, dextran sulfate, prior to its interaction with glass, displayed Fg displacement similar to untreated HK-deficient plasma.However, if Factor Xl-deficient plasma was incubated with dextran sulfate prior to exposure to glass, the Fg displacement pattern resembled normal, untreated plasma. These results suggest that the inactive cofactor form of HK (HMWKi) generated by Factor XIa (formed during extensive contact activation) does not displace Fg. Furthermore, Fg displacement was also reduced in untreated Factor Xll-deficient plasma exposed to glass, suggesting that the active cofactor form of HK (HMWKa) generated by exposure to kallikrein (during Factor Xll-dependent contact activation) may be the active participant in the Vroman Effect. The cofactor function of HK and its ability to displace Fg, therefore, appear to parallel. We also found that plasminogen or plasminogen activators were minimally involved in the Vroman Effect. Fg adsorption to glass in plasminogen-depleted HK-deficent plasma resembled Fg adsorption in a single protein system since more Fg was adsorbed and desorption failed to occur. A synergism may therefore exist between plasminogen and HK in the Vroman Effect. A better understanding of the mechanism of blood-artificial surface interaction is essential for the design of less thrombogenic biomaterials.