Application of different lupus anticoagulant diagnostic algorithms to the same assay data leads to interpretive...

Gold standard lupus anticoagulant (LA) assays and reference plasmas do not exist and detection is based on inference in a medley of coagulation assays, creating potential for interpretive discrepancies when applying different algorithms.

To investigate discrepancies from applying different algorithms to a common data set.

Diagnostic data on 311 non-anticoagulated patients LA-positive by dilute Russell's viper venom time (dRVVT) and/or dilute activated partial thromboplastin time (dAPTT) assays were employed to compare algorithms. Routine testing applied interpretive criteria from guidelines endorsing classification as LA-positive despite negative mixing tests, after exclusion of other clotting abnormalities. Integrated testing without mixing tests, and the classical algorithm where negative mixing tests preclude confirm tests, were then retrospectively applied to those data.

Initial testing showed 92/311 (29.6%) were LA-positive by dRVVT only, 156/311 (50.1%) by dAPTT only, and 63/311 (20.3%) by both assays. All dAPTT-positive plasmas remained positive with integrated testing but eight dRVVT-positives became negative. Other data suggested they were false-negatives. The classical algorithm altered 52/155 (33.5%) dRVVT and 111/219 (50.7%) dAPTT interpretations to LA-negative because of normal mixing tests, most of which were apparently weak LA in undiluted plasma.

The classical algorithm improves diagnostic specificity and confidence but risks missing some genuine LA due to false-negative mixing tests. Integrated testing can be diagnostically accurate and logistically efficient but oversimplifies complex cases. Performing mix and confirm in response to an elevated screen with their interpretation based on clinical data, coagulation screens and the LA-assay design offers a potentially valuable option.