Ruling out lupus anticoagulants with mixing test-specific cutoff assessment and the index of circulating anticoagulant

Background Lupus anticoagulant (LA) is classified in the antibody family that is recognized in antiphospholipid syndrome. Mixing tests are recommended for LA detection, and either a mixing test-specific cutoff (MTC) or index of circulating anticoagulant (ICA) is used for the interpretation. Although we previously showed MTC had higher sensitivity for LA than ICA, there are few studies investigating specificity. Objectives To investigate specificity of multiple activated partial thromboplastin time (APTT) and diluted Russell's viper venom time (dRVVT) reagents for inhibitors using plasmas with non-LA causes of prolonged clotting times, interpreted with MTC and ICA. Methods Seventy-six factor-deficient samples (either artificially prepared, hereditary deficiency, or warfarin), and 12 inhibitors (either coagulation factor inhibitors, rivaroxaban, or apixaban) were used. Samples were tested with 4 APTTs, 1 dilute APTT (dAPTT), and 2 dRVVT reagents, and all elevated screen ratios were followed up with mixing tests. Frequencies of corrected and not-corrected results were calculated. Results The frequency of MTC and ICA corrected results, suggesting factor deficiency, were 5% to 43% and 79% to 100%, respectively, except for dAPTT, where MTC and ICA performed similarly. Frequencies of MTC and ICA not-corrected results, suggesting inhibition, were 29% to 100% and 25% to 67%, respectively. Conclusions The data indicate that MTC has a tendency to generate not-corrected mixing tests in factor-deficient, warfarin, and other inhibitor samples, while ICA exhibited higher specificity. When we perform the mixing test and interpret the data, it is important to understand the characteristics of the indexes for maximizing the diagnostic potential of mixing test.