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

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. Omniplasma was spiked with rivaroxaban, apixaban, or edoxaban in a 5-604ng/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. 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 75ng/mL for all DXaIs. 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.