Antithrombin III Northwick Park: demonstration of an inactive high MW complex with increased affinity for heparin

It has been shown previously that antithrombin III Northwick Park has reduced ability to inactivate thrombin and is characterized by an additional anodal component on crossed immunoelectrophoresis (Howarth et al, 1985). We have applied plasma from an affected family member to heparin-Sepharose and eluted the antithrombin III with a salt gradient. Evidence is presented that a variant component has slightly higher affinity for heparin than normal antithrombin III. Furthermore, this variant component is present in plasma as an approximately 120,000 MW inactive antithrombin III complex that can be reduced with dithiothreitol to MW approximately 60,000, indicating disulphide bridging. Using ion-exchange chromatography, the inactive complex has been isolated and shown to migrate in the same position as the anodal peak on crossed immunoelectrophoresis.