Improved detection of lupus anticoagulants by the dilute Russell's Viper venom time

Accurate and timely detection of lupus anticoagulants (LAs) is of diagnostic and prognostic importance due to the association of persistent LAs with thrombotic disease. A review of LA screening results by kaolin clotting time and dilute Russell's Viper venom time (dRVVT) on 2843 patient samples demonstrated that only 40.7% (417 of 1024) of elevated dRVVT ratios could be interpreted as consistent with the presence of an LA by confirmatory procedures. Apart from those due to the effects of anticoagulant therapy, the remainder generated inconclusive interpretations, necessitating significant numbers of costly repeat investigations. Manipulation of dRVVT assay conditions by increasing confirmatory reagent concentration, and altering venom concentration to maintain analytical parity with the standard assay, revealed LAs not fully neutralized by confirmatory tests at standard concentrations. Further experiments were performed using Russell's Viper venom reagents from five different manufacturers to demonstrate that the findings were not a reagent-specific phenomenon. Higher detection rates were achieved using multiple conventional assays but samples remained that required a modified confirmatory test to demonstrate LA activity. A previously unreported group of LAs was identified with raised dRVVT ratios that failed to correct with any of the dRVVT assays but demonstrated significant correction with all reagents in the modified confirmatory test. Use of modified confirmatory tests enhances sensitivity and specificity, and doubles LA detection rates by dRVVT. Adoption of the technique will significantly increase cost-effectiveness of LA detection in clinical practice.