Effective production of FXIIa and thrombin by model biomaterials

The initiation of contact activation of the coagulation cascade takes place when Factor XII interacts with a procoagulant surface. Subsequent events include FXII autoactivation to the enzyme FXIIa and formation of a contact activation complex. Additional conversions result in the generation of thrombin and formation of an insoluble fibrin clot. This study examines the ability of a biomaterial to generate FXIIa and thrombin by comparing the procoagulant efficiency of glass beads to soluble aliquots of enzymes. FXIIa induced activation of coagulation saturates at surprisingly dilute concentrations (∼0.5 μg/ml), and this effect is also seen in surface and thrombin induced contact activation. Preliminary analysis of data suggests that 50 mm² glass surface area generates the equivalent of 5 ng of FXIIa, or only ∼0.0125% conversion of physiologic concentration, as well as producing the equivalent of ∼2.65 units/ml of thrombin. Addition of procoagulant (glass) surface was also found to modulate a local minimum observed in FXIIa titration curves. The results observed with FXIIa and biomaterials suggest that an investigation of the mechanisms behind FXIIa and thrombin production by biomaterials, as well as a clearer understanding of how signals propagate down the pathway, are necessary for assembling a detailed mechanism for surface activation.