Summary
A quantitative and qualitative deficiency of antithrombin III (AT III) was found in
four members of a Spanish family with thrombotic tendency. In all affected members,
levels of AT III antigen and activity (heparin cofactor activity) were reduced to
50% of the normal range. When crossed immunoelectrophoresis (CIE) was performed in
the presence of heparin, an abnormal slow-moving peak was found. Crossed immunoelectrofocusing
(CIEF) from normal and affected individuals showed that normal AT III migrated between
pH 4.9–5.3 while the AT III under study was asymetrically distributed between two
pH ranges: 4.9–5.3 and 4.6–4.8. Affinity adsorption of affected members’ plasma to
heparin-sepharose beads revealed one population of AT III in the supernatant corresponding
to the abnormal AT III, devoid of heparin cofactor activity and showing a peak between
pH range: 4.6–4.8 in CIEF.
Our data supports the view that a quantitative-qualitative deficiency was present
in the heterozygous state in all the affected family members. Both normal and abnormal
ATIII were present in plasma of the affected individuals. This abnormal ATIII was
characterized by a lack of affinity for heparin. This familial ATIII deficiency was
named ATIII Barcelona.
Key words
Antithrombin III deficiency - Variant - Heparin cofactor - Crossed immunoelectrofocusing
- Thrombosis
