title: Progressive chromogenic anti-factor Xa assay and its use in the classification of antithrombin deficiencies.
abstract: BACKGROUND
  Antithrombin (AT) is a slow-acting progressive inhibitor of activated clotting factors, particularly thrombin and activated factor X (FXa). However, the presence of heparin or heparan sulfate accelerates its effect by several magnitudes. AT deficiency, a severe thrombophilia, is classified as type I (quantitative) and type II (qualitative) deficiency. In the latter case mutations may influence the reactive site, the heparin binding-site (HBS) and exert pleiotropic effect. Heterozygous type II-HBS deficiency is a less severe thrombophilia than other heterozygous subtypes. However, as opposed to other subtypes, it also exists in homozygous form which represents a very high risk of venous thromboembolism.
  
  
  METHODS
  A modified anti-FXa chromogenic AT assay was developed which determines both the progressive (p) and the heparin cofactor (hc) activities, in parallel. The method was evaluated and reference intervals were established. The usefulness of the assay in detecting type II-HBS AT deficiency was tested on 78 AT deficient patients including 51 type II-HBS heterozygotes and 18 homozygotes.
  
  
  RESULTS
  Both p-anti-FXa and hc-anti-FXa assays showed excellent reproducibility and were not influenced by high concentrations of triglyceride, bilirubin and hemoglobin. Reference intervals for p-anti-FXa and hc-anti-FXa AT activities were 84%-117% and 81%-117%, respectively. Type II-HBS deficient patients demonstrated low (heterozygotes) or very low (homozygotes) hc-anti-FXa activity with normal or slightly decreased p-anti-FXa activity. The p/hc ratio clearly distinguished wild type controls, type II-HBS heterozygotes and homozygotes.
  
  
  CONCLUSIONS
  Concomitant determination of p-anti-FXa and hc-anti-FXa activities provides a reliable, clinically important diagnosis of type II-HBS AT deficiency and distinguishes between homozygotes and heterozygotes.
authors: Bettina
authors: B
authors: Kovács
authors: Zsuzsanna
authors: Z
authors: Bereczky
authors: Anna
authors: A
authors: Selmeczi
authors: Réka
authors: R
authors: Gindele
authors: Zsolt
authors: Z
authors: Oláh
authors: Adrienne
authors: A
authors: Kerényi
authors: Zoltán
authors: Z
authors: Boda
authors: László
authors: L
authors: Muszbek
mesh_terms: D000990:Antithrombin III / Q000032:analysis* / Q000235:genetics / Q000592:standards; D020152:Antithrombin III Deficiency / Q000145:classification / Q000175:diagnosis*; D001663:Bilirubin / Q000737:chemistry; D001780:Blood Coagulation Tests / Q000592:standards; D015951:Factor Xa / Q000737:chemistry / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D014280:Triglycerides / Q000737:chemistry
chemical_list: D006454:Hemoglobins; D014280:Triglycerides; D000990:Antithrombin III; D006493:Heparin; D015951:Factor Xa; D001663:Bilirubin