Direct oral anticoagulant adsorption: impact on lupus anticoagulant testing. Review of the literature and evaluation on spiked and patient samples
BACKGROUND: Direct oral anticoagulants (DOAC) interfere with lupus anticoagulant (LAC) testing. DOAC-StopTM (D-S) represents a preanalytical strategy to cope with this issue. OBJECTIVES: To assess D-S's ability to remove DOAC 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 (VKA,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 DOAC except apixaban. Following D-S, DOAC levels were below lower limits of quantification (LLoQs), except for apixaban at the highest concentration, and no false positive LAC was obtained. DOAC levels were below LLoQs 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, while 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 as incomplete removal may occur. Applying D-S to VKA-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.