Preliminary Evaluation of a Novel Lupus Anticoagulant Activity Assay Unaffected by Anticoagulants

In Japan, clinical laboratories commonly assess lupus anticoagulant (LA) activity using phospholipid-dependent coagulation assays as part of the diagnostic evaluation of antiphospholipid syndrome (APS). However, LA detection involves complex procedures and may yield false-positive results in patients receiving anticoagulant therapy, such as direct oral anticoagulants (DOACs). This study aimed to clarify the effects of anticoagulants on guideline-based LA testing (diluted Russell's viper venom time (dRVVT) and/or LA-sensitive activated partial thromboplastin time (APTT)) and to evaluate whether they interfere with accurate LA assessment. We also explore a simple one-step method to minimize anticoagulant interference and improve diagnostic efficiency.

We developed a one-step method for assessing LA activity by calculating the LA-sensitivity ratio (LA-SR), defined as the ratio of APTT measured using high- and low-sensitivity APTT reagents. The clinical utility of the LA-SR assay was evaluated using plasma samples from 57 patients with systemic lupus erythematosus, 74 patients with prolonged APTT, and DOAC-spiked plasmas.

The method showed agreement with the guideline-based LA testing. Of the 57 cases, 14 were LA-positive and 38 were LA-negative according to guideline-based testing. Among the 43 cases classified as LA-negative, five showed elevated LA-SR values despite negative guideline-based results. The LA-SR assay was minimally affected by DOACs, warfarin, heparin, or coagulation factor deficiencies.

This LA-SR-based method may serve as a useful screening tool for the evaluation of LA activity. A negative LA-SR result may help identify samples unlikely to have LA activity, while positive results should be interpreted cautiously and confirmed using guideline-based testing.