PB0546 - Measurement of β-antithrombin activity in healthy individuals and in patients with different types of antithrombin deficiency

Background: The β glycoform of antithrombin (AT) has higher heparin affinity than α-form and accounts for 5-10% of total AT in normal plasma. β-AT is thought to play a greater role in the prevention of thrombosis during vessel-wall injury. It may have an impact on the thrombotic risk in AT deficiency. Since measurement of this isoform is not performed routinely, the level of β-AT in these patients is unknown.

Aims: To determine the activity of total and β-AT in healthy controls and in AT deficient patients.

Methods: Anti-FXa chromogenic method in the presence of heparin and its modified version in the presence of high (1.1M) NaCl concentration were used in 50 controls and 79 patients.

Results: In the controls, the median (IQR) total AT activity was 105 (98-116)% and the β-AT activity was - as expected – 8.9 (8.2-9.2)%. The calculated β-AT percentage of total AT activity (β-AT%) was 8.3 (7.9-8.8)%. In type II heparin binding site (IIHBS) deficient AT Budapest 3 heterozygotes (n=50) the total AT activity, the β-AT activity and the β-AT% were 58 (54-61)%, 8.4 (8.2-8.9)% and 14.5 (13.9-15.6)%, respectively. These results were in concordance with those measured in AT type IIHBS Basel and Padua (n=2) patients. In AT Budapest 3 homozygotes (n=9) total AT activity, β-AT activity and β-AT% were 17 (15-26)%, 7.4 (6.8-10.2)% and 41.6 (38.6-48.0)%, respectively. On the contrary, in patients having type I AT defect – although total AT activity was comparable with type IIHBS heterozygotes, 52 (46-53)% - the β-AT activity was significantly lower, 6.8 (6.5-7.2)%.

Conclusion(s): Our results show that – while in type I quantitative AT deficiency the total and β-AT activity are proportionally decreased - the activity of β-AT is less affected by type IIHBS AT mutations. These results support the clinical observations of less severe thrombotic phenotype in type IIHBS deficiency.