The superiority of anti-FXa assay over anti-FIIa assay in detecting heparin-binding site antithrombin deficiency

Abstract

Objectives: Antithrombin is a progressive inhibitor of active factor X (FXa) and thrombin (FIIa). Its effect is 500- to 1,000-fold accelerated by heparin or heparan sulfate. Heterozygous type I (quantitative) and most type II (qualitative) antithrombin deficiencies highly increase the risk of venous thromboembolism (VTE), while homozygous mutations are lethal. The functional defect affecting the heparin-binding site confers moderate risk of VTE to heterozygous and high risk of VTE to homozygous individuals.

Methods: Antithrombin activity assays based on the inhibition of FIIa and FXa were compared for their efficiency in detecting heparin-binding site defects.

Results: With a single exception, in heterozygotes for heparin-binding site defects (n = 20), anti-FIIa activities remained in the reference interval, while anti-FXa activities were uniformly decreased. In individuals who were homozygous for heparin-binding site mutations (n = 9), anti-FIIa activities were in the range of 48% to 80%; the range of anti-FXa activities was 9% to 25%. Anti-FIIa and anti-FXa activities in type I deficiencies and type II pleiotropic deficiency did not differ significantly.

Conclusions: Anti-FXa antithrombin assay is recommended as a first-line test to detect type II heparin-binding site antithrombin deficiency.

Keywords: Antithrombin; Antithrombin deficiency; Heparin-binding site defect; Thrombophilia.