Summary
Abnormal antithrombin III (AT III) was found in the plasma of a 31-year-old female
who suffered from recurrent thrombotic episodes. Heparin cofactor activity was 28%
of normal and undetectable when measured by inhibition of thrombin and factor Xa (F.
Xa), while both progressive antithrombin and antifactor Xa activities were normal.
The concentration of plasma AT III antigen was 37 mg/dl. Analysis by crossed-immunoelec-
trophoresis (CIE) in the presence of heparin and affinity chromatography on heparin-Sepharose
revealed that the propositus’ AT III did not bind to heparin. When heparin cofactor
II (HC II) was removed from propositus’ plasma, heparin cofactor activity of AT III
was not detected. Thus, HC II seemed to account for the plasma heparin cofactor activity
found in the presence of thrombin. The patient’s parents and three of her brothers
demonstrated qualitative abnormality of AT III; heparin cofactor activity was 30-50%
of normal levels in the presence of both thrombin and F. Xa. These findings indicate
that the propositus’ AT III lacks affinity for heparin and the mode of its inheritance
seems to be autosomal dominant and, hence, the propositus would be a homozygote. For
this variant, the name of AT III Kumamoto is proposed.
Key words
Antithrombin III - Abnormal antithrombin III - Heparin cofactor activity - Thrombosis
- Heparin cofactor II
