Adverse effects of direct oral anticoagulant (DOAC) therapy on APTT cross-mixing test determination

Abstract

Lupus anticoagulant (LA) is defined as an immunoglobulin that inhibits phospholipid-dependent clotting reactions without inhibiting the activity of individual clotting factors. Detection of LA activity by phospholipid-dependent coagulation assay is one of the laboratory test findings in the antiphospholipid syndrome (APS) diagnostic criteria. among LA screening tests, APPT-based cross-mixing tests are common tests in clinical laboratories. The cross-mixing test differentiates whether the prolonged clotting time is due to a coagulation factor deficiency, coagulation factor inhibitor, or LA, based on the coagulation plot pattern. Recent clinical studies suggest that patient plasma on direct oral anticoagulant (DOAC) therapy may influence LA determination by APTT-based cross-mixing tests. This study investigated the effects of four DOACs (dabigatran, rivaroxaban, edoxaban, and apixaban) on APPT-based cross-mixing tests, the efficacy of DOAC removers, and the usefulness of confirmatory testing using Staclot LA. As a result, many of the DOAC model therapy plasma samples were judged to be false positive for LA, and treatment with a DOAC remover may not have led to correct results. On the other hand, an LA confirmation test using the addition of hexagonal (II) phase phospholipid correctly determined that all cases were LA negative. The results of this study suggest that when conducting LA tests on patients undergoing DOAC therapy, it is important to perform a confirmation test using Staclot LA reagent.