Mixing studies for lupus anticoagulant: mostly no, sometimes yes

Mixing tests have long been a mainstay in the lupus anticoagulant (LA) testing armoury of screen, mix and confirm assays. If a sample with an elevated screening test does not evidence inhibition in the mixing test, the search for an LA is halted and a different diagnostic pathway embarked upon. Recent years have seen studies evidencing sometimes high frequencies of false-negative mixing tests with perhaps sinister implications for missed diagnoses and skewed patient management. Issues such as the dilution effect, between-reagent sensitivity and specificity differences, variability of normal pooled plasma (NPP) quality and suitability and interpretive inconsistencies all contribute to questioning the reliability of mixing tests and their pivotal place in the LA assay hierarchy. The advent of integrated testing, where phospholipid-dependence is demonstrated or excluded prior to any attempt to evidence inhibitory properties with a fallible analytical principle, provides an alternative path to LA detection. In the absence of other causes of elevated clotting times, LA assay screen and confirm discordance is sufficient to secure a laboratory diagnosis of the presence of an LA, leaving the mixing test in a supplementary yet valuable role when further diagnostic discrimination is required.