title: An international multicentre-laboratory evaluation of a new assay to detect specifically lupus anticoagulants dependent on the presence of anti-beta2-glycoprotein autoantibodies.
abstract: BACKGROUND
  Antiphospholipid syndrome (APS) is diagnosed by the simultaneous presence of vascular thrombosis and/or pregnancy morbidity and detection of antiphospholipid antibodies in plasma.
  
  
  OBJECTIVE
  We have shown that prolongation of clotting time by anti-beta2-glycoprotein I (beta2GPI) antibodies correlates better with thrombosis than a positive classic lupus anticoagulant (LAC) assay in a single center study. To confirm or falsify this finding we have conducted a multicenter study.
  
  
  RESULTS
  In 325 LAC-positive samples, we found that the beta2GPI-dependent LAC correlated 2.0 times better with thrombosis than the classic LAC assay. Although significant, this was a minimal improvement compared with the 'classic' LAC. It was published that calcium influences the behavior of anti-beta2GPI antibodies in coagulation assays. To investigate whether calcium plays a role in the present study, we divided the patient population into two groups: (i) blood was collected in 0.109 m sodium citrate and (ii) blood was drawn in 0.129 m sodium citrate as anticoagulant. We found that a positive result with the beta2GPI-dependent LAC assay correlated better with thrombosis [odds ratio (OR): 3.3, 95% confidence interval (CI) 1.9-5.8] when 0.109 m sodium citrate was used compared with 0.129 m sodium citrate (OR: 0.4, 95% CI 0.1-1.1).
  
  
  CONCLUSIONS
  We were able to confirm in an international multicenter study that a positive result in a beta2GPI-dependent LAC assay correlates better with thrombosis than the classic LAC assay, but that the assay needs further study as it is sensitive to external factors such as the sodium citrate concentration used as anticoagulant in the test sample.
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center, Utrecht, the Netherlands. b.delaat@umcutrecht.nl
authors.forename: B
authors.initials: B
authors.lastname: De Laat
authors.forename: R H W M
authors.initials: RH
authors.lastname: Derksen
authors.forename: G
authors.initials: G
authors.lastname: Reber
authors.forename: J
authors.initials: J
authors.lastname: Musial
authors.forename: J
authors.initials: J
authors.lastname: Swadzba
authors.forename: B
authors.initials: B
authors.lastname: Bozic
authors.forename: S
authors.initials: S
authors.lastname: Cucnik
authors.forename: V
authors.initials: V
authors.lastname: Regnault
authors.forename: R
authors.initials: R
authors.lastname: Forastiero
authors.forename: B J
authors.initials: BJ
authors.lastname: Woodhams
authors.forename: Ph G
authors.initials: PG
authors.lastname: De Groot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001118:Argentina; D001323:Autoantibodies / Q000097:blood*; D001777:Blood Coagulation; D001800:Blood Specimen Collection / Q000379:methods; D002648:Child; D002951:Citrates / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D005260:Female; D006801:Humans; D016015:Logistic Models; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010314:Partial Thromboplastin Time; D011933:Reagent Kits, Diagnostic; D000077559:Sodium Citrate; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000276:immunology; D055815:Young Adult; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D000925:Anticoagulants; D001323:Autoantibodies; D002951:Citrates; D016682:Lupus Coagulation Inhibitor; D011933:Reagent Kits, Diagnostic; D053482:beta 2-Glycoprotein I; D000077559:Sodium Citrate