Reagent-specific anti-Xa DOAC safety cutoffs can be established using multiple LMWH-calibrated anti-Xa assays

OBJECTIVES: Fast estimations of direct oral anticoagulant (DOAC) plasma concentrations are useful in ruling out clinically significant concentrations before urgent surgical interventions. DOAC-specific anti-factor Xa (anti-Xa) assays are time consuming and not available 24/7 in most hospitals. Anti-Xa assays calibrated with low-molecular weight heparins (LMWHs) are widely available 24/7 and could give concentration estimations for anti-Xa DOACs (DXaIs). This study aimed to determine whether LMWH-calibrated anti-Xa assays could establish thresholds corresponding to DXaI concentrations associated with non-increased bleeding risk. METHODS: Omniplasma was spiked with rivaroxaban, apixaban, or edoxaban in a 5-604 ng/mL range. One pooled patient sample was included per DXaI. Samples were analysed in 18 hospital laboratories, using 5 different analyser-reagent combinations (Stago Liquid anti-Xa on STA-R Max2/3, HemosIL Liquid anti-Xa on ACL-TOP350/550, Innovance Heparin on CS2500/CN3000, Biophen Heparin LRT on CS2500/CS5100, Roche anti-Xa on Cobas t511 analysers). Samples were analysed using local LMWH anti-Xa assay protocols using local reagent lots. Delta optical density and "LMWH" anti-Xa-activity were reported. DXaI concentrations were confirmed using liquid chromatography with tandem mass spectrometry detection. RESULTS: Large differences in DXaI sensitivity between reagent groups were observed, which prevent formulation of universal threshold values for non-increased risk of bleeding. However, reagent-specific threshold values can be established with the exception of the Hyphen reagent group, due to high interlaboratory variability. Within analyser-reagent groups, a good correlation between spiked DXaI concentrations and "LMWH" activity assay readout is observed, permitting conversion between the two units up to 75 ng/mL for all DXaIs. CONCLUSIONS: Widely available rapid low-to-moderate DXaI concentration estimation can be achieved using LMWH-calibrated anti-Xa assays. Potential applications include ruling out clinically relevant DXaI concentrations before surgery and screening for the presence of a factor Xa inhibitor, but not specific DXaI monitoring.