Newly developed dilute Russell's viper venom reagents for lupus anticoagulant detection with improved specificity

Background Dilute Russell's viper venom time (dRVVT) is indispensible in lupus anticoagulant (LA) detection yet commercial reagents from different suppliers perform variably, no gold standard assays exist and therapeutic anticoagulation interference is problematic. Objective The objective of this study was to compare a new formulation dRVVT with two currently available dRVVTs. Materials and methods Life Diagnostics (LD) dRVVT and Stago PTT-LA were routinely used for lupus anticoagulant detection, plus Taipan snake venom time/ecarin time (TSVT/ET) for patients on warfarin or rivaroxaban. Siemens dRVVT and the new HYPHEN BioMed (HBM) dRVVT were tested with 193 patient samples. Group 1, 59 non-anticoagulated patients (NAPs) LA-positive in LD dRVVT; Group 2, 15 PTT-LA-positive/dRVVT-negative NAPs; Group 3, 24 LA-positive warfarinized patients; Group 4, 13 patients on rivaroxaban; Group 5, 62 LA-negative thrombotic NAPs; Group 6, 20 warfarinized, non-antiphospholipid syndrome patients. Results Accepting that the Life Diagnostics reagents were acting as a pseudo-gold standard, Siemens dRVVT detected 56/59, (95%) Group 1 LA and HBM dRVVT 46/59, (76%), one each from Group 2, and Siemens dRVVT detected one in Group 5. The lower HBM dRVVT detection rate mainly concerned weaker LA, where between-reagent concordance is problematic. All Group 3 patients appeared LA-positive in undiluted plasma with Siemens dRVVT, as did 16/24 (67%) with HBM dRVVT but the fewer LA-positives in mixing tests better mapped to clear LA-positives with LD dRVVT. LD and Siemens dRVVTs exhibited 87% and 95% false-positivity for Group 6 whilst HBM dRVVT had none. Increasing the cut-off improved accuracy. Applying higher cut-offs improved accuracy in Group 4 patients. Conclusion HBM dRVVT exhibited improved specificity, mainly due to less interference by anticoagulation, but reduced sensitivity, compared to the other dRVVTs employed.