Neutralising rivaroxaban induced interference in laboratory testing for lupus anticoagulant (LA): A comparative study using DOAC Stop and andexanet alfa

Emmanuel J Favaloro, Grace Gilmore, Sandya Arunachalam, Soma Mohammed, Ross Baker

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34 Citations (Scopus)


INTRODUCTION: Lupus anticoagulant (LA) investigation in patients on anticoagulant therapy is problematic. Rivaroxaban in particular causes significant interference, prolonging both LA screening and confirmation tests, and falsely raising LA screen/confirm ratios, leading to potential false identification of LA. The Russell Viper Venom Time (RVVT) assay, key to the investigation of LA, is especially sensitive to rivaroxaban.

MATERIALS AND METHODS: We assessed cross laboratory (n = 82) testing of four samples to investigate whether rivaroxaban induced interference in LA testing could be neutralised. Testing was performed blind to sample type. The samples comprised: (A) A pool of normal plasma (LA-negative control); (B) sample A spiked with rivaroxaban (200 ng/mL) to create rivaroxaban-induced interference (LA 'false' positive sample); (C) sample B subsequently treated with a commercial 'DOAC-neutraliser' (DOAC Stop); (D) sample B treated with andexanet alfa (200 μg/mL).

RESULTS: As expected, the rivaroxaban-spiked sample (B) caused prolongation of most LA-tests, and also generated a falsely prolonged RVVT screen/confirm ratio (median 1.37, compared to 0.97 for sample A). The sample (C) treated with DOAC Stop evidenced a correction in LA-test clotting times, as well as neutralising the false positive LA (median RVVT screen/confirm ratio of 0.99). Although the andexanet alfa treated sample (D) also yielded a low median RVVT screen/confirm ratio of 0.88, it did not fully correct LA-test clotting times. Consistent with test findings, all laboratories interpreted samples A and C as being LA-negative. For sample B (rivaroxaban), 45.3% identified this as LA positive, and 38.7% identified LA interference. Most (61.3%) also identified sample D as LA negative, with the remainder (38.7%) identifying LA interference.

CONCLUSIONS: DOAC Stop was able to neutralise the false LA activity induced by rivaroxaban, both in terms of clot-times and LA ratios. In contrast, whilst andexanet alfa negated the rivaroxaban-prolonged LA-ratio, it did not fully correct clot-times, leaving some residual LA interference, and requiring additional testing to investigate prolonged clotting times.

Original languageEnglish
Pages (from-to)10-19
Number of pages10
JournalThrombosis Research
Early online date23 May 2019
Publication statusPublished - Aug 2019


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