title: The superiority of anti-FXa assay over anti-FIIa assay in detecting heparin-binding site antithrombin deficiency.
abstract: OBJECTIVE
  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.
authors.affiliation: Clinical Research Center, University of Debrecen, Medical and Health Science Center, 98 Nagyerdei Krt, 4032 Debrecen, Hungary; muszbek@med.unideb.hu.
authors.forename: Bettina
authors.initials: B
authors.lastname: Kovács
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bereczky
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Oláh
authors.forename: Réka
authors.initials: R
authors.lastname: Gindele
authors.forename: Adrienne
authors.initials: A
authors.lastname: Kerényi
authors.forename: Anna
authors.initials: A
authors.lastname: Selmeczi
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Boda
authors.forename: László
authors.initials: L
authors.lastname: Muszbek
mesh_terms: D020152:Antithrombin III Deficiency / Q000097:blood / Q000175:diagnosis*; D001780:Blood Coagulation Tests / Q000379:methods; D015951:Factor Xa / Q000032:analysis; D065427:Factor Xa Inhibitors; D005260:Female; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008297:Male; D011485:Protein Binding; D011516:Prothrombin / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: D065427:Factor Xa Inhibitors; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa
keywords: Antithrombin; Antithrombin deficiency; Heparin-binding site defect; Thrombophilia