Studies of the heterogeneity of antithrombin III concentrates

Abstract
The biological activities of antithrombin III (At III) concentrates, prepared by several manufacturers for clinical use, were compared by 3 assay methods, and their heparin-binding properties studied by crossed immunoelectrophoresis and heparin affinity chromatography. Concentrates from 2 of the 4 manufacturers showed discrepancies between assay methods, with concentrations by heparin co-factor assays significantly lower than those by immunological and progressive antithrombin methods. Heterogeneity was also found by heparin binding studies, with about half the total At III antigen in these concentrates being unable to bind to heparin. These results confirm previous findings of heterogeneity in At III concentrates and show that some concentrates contain substantial amounts of altered At III molecules in which the heparin-binding site was denatured but the thrombin-neutralizing site left largely intact.