In vitro evaluation of heparinized cuprophan hemodialysis membranes

Cuprophan hemodialysis membranes can be heparinized using N,N'- carbonyldiimidazole (CDI) as a coupling agent. In this study, the characteristics of heparinized Cuprophan membranes have been evaluated. After immobilization, heparin partially retained its biologic activity. An anticoagulant activity of 12.4 ± 4.2 mU/cm² was measured using a thrombin inactivation assay. Immobilized heparin also displayed an anti-complement activity. After contact with human serum, heparinized Cuprophan induced no generation of significant amounts of fluid phase terminal complement complex (TCC), whereas untreated Cuprophan induced the generation of substantial amounts of TCC. Heparinization did not affect the permeability of Cuprophan for model solutes with molecular weights up to 12,000 g/mol except for sulfobromophthalein sodium salt. The permeability of Cuprophan for sulfobromophthalein sodium salt was slightly decreased after heparinization. The ultrafiltration rate of Cuprophan increased by about 30% after heparinization, probably owing to an increased swelling of the membrane in water. Heparinized Cuprophan incubated in phosphate-buffered saline at 37°C showed some release of heparin. These amounts of released heparin, however, were very low as compared to the amounts of heparin which are systemically administered during clinical hemodialysis treatment. It is concluded that Cuprophan membranes heparinized by means of the CDI-activation procedure are highly promising for application in hemodialyzers to be used for the treatment of patients with reduced or without systemic administration of heparin.