title: Further evidence of false negative screening for lupus anticoagulants.
abstract: BACKGROUND
  Accurate and timely detection of lupus anticoagulants (LA) is of diagnostic and prognostic importance due to the association of persistent LA with thrombotic disease. Antibody heterogeneity and assay variability complicate LA detection and weak antibodies can go undetected.
  
  
  METHODS
  Screen and confirm assays on equal volume mixing studies were performed on known LA using dilute Russell's viper venom time (DRVVT), dilute activated partial thromboplastin time (DAPTT) and activated seven lupus anticoagulant (ASLA) assay. Two established calculations for phospholipid dependence were applied to ascertain whether any antibodies diluted to within screening test reference ranges maintained a significant difference between screen and confirm results sufficient to imply LA activity. We then performed confirmatory tests on neat plasma samples from patients with thrombotic disease whose screening tests were within reference ranges.
  
  
  RESULTS
  Forty nine of 155 DRVVT positive LA were conventionally positive in the mixing studies and 8 of the 106 negative mixing studies showed significant screen and confirm test discordance. This was the case for 21 of 56 negative DAPTT mixing studies and 2 of 39 negative ASLA mixing studies. Performance of confirm assays on the neat plasma samples with screen results within reference ranges revealed possible LA activity in 19 of 166 DRVVT results, 63 of 184 DAPTT results and 9 of 117 ASLA results.
  
  
  CONCLUSIONS
  LA activity can be demonstrated by assessment of screen and confirm data irrespective of screening test elevation above a reference range. Other workers have demonstrated this phenomenon in APTT using different study designs and it may be that standard interpretation criteria warrant re-assessment.
authors.affiliation: Centre for Haemostasis and Thrombosis, Haemophilia Reference Centre, 1st Floor North Wing, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, England. gary.moore@gstt.nhs.uk
authors.forename: G W
authors.initials: GW
authors.lastname: Moore
authors.forename: A
authors.initials: A
authors.lastname: Henley
authors.forename: C K
authors.initials: CK
authors.lastname: Greenwood
authors.forename: S
authors.initials: S
authors.lastname: Rangarajan
mesh_terms: D005188:False Negative Reactions; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D010314:Partial Thromboplastin Time; D012016:Reference Values
chemical_list: D016682:Lupus Coagulation Inhibitor