Permeability of a heparin-polyvinyl alcohol hydrogel to thrombin and antithrombin III

The diffusivities of thrombin and antithrombin III in a heparin-polyvinyl alcohol hydrogel were estimated and used to demonstrate that diffusion limits the effectiveness of the immobilized heparin in the interior of such hydrogels. Diffusivities were calculated from permeabilities and partition coefficients measured with films in a diffusion chamber apparatus. The diffusion coefficients were estimated to be 6 +/- 4 X 10(-8) cm2/s for thrombin and 4 +/- 2 X 10(-8) cm2/s for antithrombin III in 10% gel membranes with or without immobilized heparin. Using the diffusivity of thrombin and a Thiele-type modulus, the effectiveness factor of a spherical heparin-PVA bead used to accelerate the inactivation of thrombin by antithrombin III was found to be 4-9% (diameter range 250-150 micron). While indicating that diffusion of thrombin limited the full utilization of the immobilized heparin, these values for the effectiveness factor could not completely account for the low apparent heparin activity (0.2%) in a thrombin time test of heparin-PVA "beads" (J. Biomed. Mater. Res., 17, 359 (1983]. Other factors such as the immobilization chemistry or the diffusion of thrombin-antithrombin III complex must be considered for a full explanation of the thrombin time results.