How surface‐bound drugs inhibit thrombus formation

Abstract

AbstractThis article presents the new concept that surface‐bound drugs can remove coagulation promoters from the bloodstream and thus produce much needed improvement in the surface thromboresistance of polymeric devices such as catheters, vascular grafts, and artificial organs. For example, calcium plays a central role in promoting coagulation, which suggests that surface thromboresistance could be improved by bonding a polymer to a calcium chelator which removes calcium from circulation. This technique has been tried and found successful in animal tests using hydroxyproline as the calcium chelator (Wilson and Jones: Biomater. Artif. Organs 17:437–445, 1989. An alternative design for a thromboristance polymer is proposed: Chemically bond a commercial polymer to a suitable drug containing cationic groups capable of complexing blood coagulation factors and rendering them inactive. The feasibility of this approach is based on two lines of evidence: (1) Several blood coagulation factors are routinely isolated by complexation on ion exchange resins containg cationic groups (tertiary amines). (2) A number of polymers containing cationic groups (tertiary amines) have been patented on the basis of their thromboresistance. In this article an ion exchange equilibrium is postulated between each anionic coagulation factor adsorbed on the polymer and dissolved in the liquid phase, with the surface affinity of each anionic factor being greater the more cationic (basic) the polymer surface. Data on the competitive adsorption of proteins on cationic polymers have been analyzed mathematically. The results suggest more attention should be given to cation/anion interactions in studies of polymeric thromboresistance and protein adsorption).