Thromb Haemost 1986; 56(03): 349-352
DOI: 10.1055/s-0038-1661681
Original Article
Schattauer GmbH Stuttgart

Characterization of an Abnormal Antithrombin (Milano 2) with Defective Thrombin Binding

A Tripodi
The A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, University of Milano, Italy
,
A Krachmalnicoff
The A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, University of Milano, Italy
,
P M Mannucci
The A. Bianchi Bonomi Hemophilia and Thrombosis Center and Institute of Internal Medicine, University of Milano, Italy
› Institutsangaben
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Publikationsverlauf

Received 20. Juni 1986

Accepted after revision 12. September 1986

Publikationsdatum:
18. Juli 2018 (online)

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Summary

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 halfnormal 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 α-thrombin immobilized on sepharose beads revealed defective binding of the anti thrombin 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.