Thrombogenicity of an artificial surface is decrease by the antiplatelet agent ditazol

Porous fibres made of synthetic polymers entrap enzymatic systems without altering their biological activity. Such fibres inserted in extracorporeal circuits have a potential clinical applicability to remove toxic substances involved in the pathogenesis of acute liver failure. Since platelets adhere extensively when fibres are exposed to human blood, the possibility was evaluated to affect thrombogenicity by coupling the fibres with antiplatelet agents. A preliminary screening carried out in vitro by means of a model of platelet retention to plastic columns filled with treated and untreated fibres showed that ditazol was highly effective in reducing retention. Ditazol was further evaluated with more sensitive experimental models involving 51Cr labelled platelets. Platelets adhered massively within the first minutes to untreated fibres wrapped around a bob rotating in heparinized blood, whereas adhesion decreased significantly when fibres were treated with ditazol. Heparinized blood flowing in a circuit by means of a pump insuring a constant flow rate of 500 ml/min was filtered through a cartridge inserted in the circuit and filled with fibres. Adhesion of 51Cr platelets to treated fibres was significantly lower than to untreated fibres. Scanning electron microscopy showed scattered individual platelets adhering to treated fibres, whereas large aggregates formed on the untreated fibres. These findings indicate that stable coupling of an antiplatelet agent to synthetic polymers markedly reduce thrombogenicity.