Further evidence of false negative screening for lupus anticoagulants

IntroductionAccurate 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.MethodsScreen 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.ResultsForty 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.ConclusionsLA 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.