title: Characterization of an abnormal antithrombin (Milano 2) with defective thrombin binding.
abstract: Four members of an Italian family (two with histories of venous thromboembolism) had a qualitative defect of antithrombin III reflected by normal antigen concentrations and half-normal antithrombin activity with or without heparin. Anti-factor Xa activities were consistently borderline low (about 70% of normal). For the propositus' plasma and serum the patterns of antithrombin III in crossed-immunoelectrophoresis with or without heparin were indistinguishable from those of normal plasma or serum. A normal affinity of antithrombin III for heparin was documented by heparin-sepharose chromatography. Affinity adsorption of the propositus' plasma to human alpha-thrombin immobilized on sepharose beads revealed defective binding of the antithrombin III to thrombin-sepharose. Hence the molecular defect of this variant appears to be at the active site responsible for binding and neutralizing thrombin, thus accounting for the low thrombin inhibitory activity.
mesh_terms: D000328:Adult; D000990:Antithrombin III / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D007558:Italy; D008297:Male; D011485:Protein Binding; D013917:Thrombin / Q000378:metabolism*; D013923:Thromboembolism / Q000235:genetics
chemical_list: D000990:Antithrombin III; D013917:Thrombin