Heparin-Coated Surfaces that bind Antithrombin have Reduced Platelet Reactivity

 

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Surfaces with heparin bound by covalent linkage react with platelets but are passivated by prior exposure to platelet free plasma (PFP), provided they are capable of adsorbing antithrombin III (AT). For example, heparin-agarose beads induce platelet adhesion and aggregation, which are reduced by preincubation of the beads with PFP, but PFP depleted of AT is not effective. The degree of passivation of the beads parallels their removal of AT from PFP. The beads are also passivated by a solution of purified AT.

Furthermore heparin-polymethyl acrylate copolymers made by radical polymerization initiated by Ce⁴⁺ bind AT, as demonstrated by measurement of AT remaining in solution after adsorption or eluted from the surface after plasma incubation. On such a surface, AT is activated just as by heparin in solution, measured by the ability of heparinized beads to inactivate thrombin (S-2160 chromogenic tripeptide substrate assay) in the presence of AT and by lack of inactivation of thrombin with AT-poor plasma and return of inactivating effect when AT is added back.

Aggregation of platelets by specific heparin fractions in solution appears to be an analogous phenomenon, which is inhibited by antithrombin.