Characterization of an abnormal antithrombin (Milano 2) with defective thrombin binding
Tripodi, A.; Krachmalnicoff, A.; Mannucci, P.M.
Thrombosis and Haemostasis 56(3): 349-352
1986
ISSN/ISBN: 0340-6245 PMID: 3563966 Document Number: 274393
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-immunoelectrophorses 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.