Lupus anticoagulant mixing tests for multiple reagents are more sensitive if interpreted with a mixing test-specific cut-off than index of circulating anticoagulant

Res Pract Thromb Haemost. 2017 Dec 23;2(1):105-113. doi: 10.1002/rth2.12069. eCollection 2018 Jan.

Abstract

Background: Lupus anticoagulant (LA) is classified in the antibody family that is recognized as antiphospholipid antibodies. Guidelines for LA detection recommend mixing test interpretation with either a mixing test specific cut-off (MTC) or index of circulating anticoagulant (ICA). We previously evidenced that MTC was superior to ICA in detecting the in vitro inhibition of LA with a single dilute APTT (activated partial thromboplastin time) and dRVVT (diluted Russell's viper venom time) pairing.

Objectives: The objective in the present study was to compare the LA diagnostic effectiveness of MTC and ICA by multiple APTT and dRVVT reagents.

Methods: One hundred-five samples from non-anticoagulated patients positive for LA in the dilute APTT (dAPTT) and dRVVT reagent pairing employed for diagnostic examination were performed by undiluted and in a 1:1 mix with normal pooled plasma with four additional APTT reagents and another dRVVT reagent (dRVVT B).

Results: Frequencies of MTC and ICA positivity were determined from samples LA positive in undiluted plasma. MTC positivity in mixing test were 63%, 77%, 80%, 84%, 46%, 81%, and 72% in 4 APTT, dAPTT and 2 dRVVT, respectively. ICA positivity were 47%, 67%, 58%, 54%, 42%, 47%, and 29%, respectively. There were no samples of ICA-positive/MTC-negative with any reagent.

Conclusions: The data indicate that MTC is superior to ICA for LA detection in mixing tests in multiple reagents and reagent types. Although mixing tests may make weak LA samples appear negative, the efficacy of LA detection can be improved by the method to interpret the results.

Keywords: activated partial thromboplastin time; antiphospholipid antibodies; antiphospholipid syndrome; diluted Russell's viper venom time; lupus anticoagulant.