Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients

BACKGROUND: Oral anticoagulation compromises conventional lupus anticoagulant (LA) screening assays. Mixing studies can counteract the oral anticoagulant effect but the dilution reduces sensitivity and can generate false negative results. A firm diagnosis can be made from mixing studies when an elevated screen ratio is accompanied by a confirm ratio that generates significant correction to demonstrate phospholipid dependence, but also returns into the reference range, indicating complete normalisation of the oral anticoagulant effect. Taipan snake venom time (TSVT) with Ecarin time (ET) as a confirmatory test comprises an oral anticoagulant insensitive LA detection system and this study investigates the potential impact on detection rates when coupled with mixing studies on standard assays. METHODS: Eighty patients known to have LA who were receiving oral anticoagulation were tested with TSVT/ET and 1:1 mixing studies with normal plasma by dilute Russell's viper venom time (DRVVT) and dilute activated partial thromboplastin time (DAPTT) to assess detection rates by single and multiple assays. RESULTS: Thirty three of the 80 samples from known LA positive patients were positive in all three assays and 15 were positive in combinations of DRVVT, DAPTT or TSVT/ET. The remainder were positive in only one assay; 12 by DRVVT, 4 by DAPTT and 16 by TSVT/ET. Although all DRVVT and DAPTT positive mixing studies generated significant correction of the screen ratio by the confirm ratio, not all confirm ratios corrected back into the reference range. This was the case for 87.5% of the DRVVT results, 44.7% of the DAPTT results and 13.3% of the TSVT/ET positive mixing tests. CONCLUSION: Addition of TSVT/ET screening for LA in orally anticoagulated patients could increase diagnostic efficacy either by detecting antibodies diluted in the mixing tests of conventional assays or those that do not react in DRVVT or DAPTT. Additionally, TSVT/ET can affirm the presence of a LA where conventional assay mixing tests may not have fully counteracted the oral anticoagulant effect but confirmatory test correction suggests the presence of a LA.