Ontario M5S IA4, Caiiadu
The diffusivities of thrombin and antithrombin I11 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 cm'/s for thrombin and 4 t 2 x lo-" cm'/s for antithrombin 111 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 I11 was found to be 4 9 % (diameter range 250-105 pm). 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" (I. Bionied. Muter.
Res., 17, 359 (1983)). Other factors such as the immobilization chemistry or the diffusion of thrombin-antithrombin 111 complex must be considered for a full explanation of the thrombin time results.