Direct Oral Anticoagulant Adsorption: Impact on Lupus Anticoagulant Testing—Review of the Literature and Evaluation on Spiked and Patient Samples

Abstract

Background Direct oral anticoagulants (DOACs) interfere with lupus anticoagulant (LAC) testing. DOAC-Stop (D-S) represents a preanalytical strategy to cope with this issue. Objectives To assess D-S's ability to remove DOACs from plasma and overcome DOAC interference in LAC assays and to evaluate D-S's applicability in a representative patient cohort with routine LAC request. Methods Apixaban (30-933 ng/mL), edoxaban (31-1060 ng/mL), rivaroxaban (35-1020 ng/mL), and dabigatran (20-360 ng/mL) were spiked to normal plasma. Aliquots were treated with D-S or untreated before DOAC and LAC testing. Patient samples containing DOAC (n = 43), vitamin K antagonists (n = 25), heparins (n = 21), or no anticoagulants (n = 63) were tested for LAC before and after D-S. Results Spiking experiments revealed false-positive LAC from low concentrations of DOACs except for apixaban. Following D-S, DOAC levels were below lower limits of quantification, except for apixaban at the highest concentration, and no false-positive LAC was obtained. DOAC levels were below lower limits of quantification after D-S in 39/43 DOAC-containing patient samples. For 23/29 LAC-positive DOAC-containing samples, LAC tests became negative after D-S, whereas 3/6 samples remaining positive were from patients with (high probability for) antiphospholipid syndrome. In the non-DOAC-treated groups, LAC changed from positive to negative in 10 and vice versa in 2 cases. Conclusions D-S limits DOAC interference in LAC assays. DOAC concentration measurement should be performed in D-S treated samples because incomplete removal may occur. Applying D-S to vitamin K antagonist-containing, heparin-containing, or not-anticoagulated samples may lead to erroneous LAC results. Therefore, D-S should only be used in plasma from DOAC-treated patients.