Mixing test specific cut-off is more sensitive at detecting lupus anticoagulants than index of circulating anticoagulant

• Interpreting LA mixing tests with MTC detects more LA than ICA.
• Some LA can be detected without mixing tests.
• LA manifestation in mixing tests appears to be a function of more than just potency.

IntroductionRecent guidelines for lupus anticoagulant (LA) detection recommend mixing test interpretation with either a mixing test-specific cut-off (MTC) or index of circulating anticoagulant (ICA). Few studies directly compare efficacy of these approaches. We retrospectively applied MTC and ICA assessment to raw data of 350 LA-positive plasmas from non-anticoagulated patients to compare detection rates of inhibition.Materials and methodsScreen and confirm dRVVT and dilute APTT assays were performed on undiluted plasma and 1:1 mixtures with normal pooled plasma. Samples were considered LA-positive if one or both screening test ratios were elevated and corrected by ≥ 10% with the confirmatory test. Mixing tests were assessed against locally derived cut-offs for MTC (dRVVT > 1.13, dAPTT > 1.15) and ICA (dRVVT > 11.9%, dAPTT > 13.2%).Results105 of 350 (30%) were positive in dRVVT and dAPTT, 109/350 (31.1%) were dRVVT positive only and 136/350 were dAPTT positive only (38.9%), from undiluted plasma results. Of the 214 dRVVT positive plasmas, 53 (24.8%) were negative for inhibition by MTC and 65 (30.4%) negative by ICA. Of the 241 dAPTT positive plasmas, 48 (19.2%) were negative by MTC and 97 (40.2%) negative by ICA.ConclusionWhilst integrated testing often detects LA without mixing tests they are diagnostically useful in certain circumstances. Thus, it is valuable to maximise mixing test interpretation as the dilution can lead to false-negative results. These data on a large cohort of LA-positive plasmas reveal that, with the reagents and equipment employed, MTC is superior to ICA in detecting the in vitro inhibition of LA.