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.
Keywords
Congenital thrombosis - Anti thrombin III - Deep-vein thrombosis
