Comparison of the DOAC Dipstick Test on Urine Samples With Chromogenic Substrate Methods on Plasma Samples in Outpatients Treated With Direct Oral Anticoagulants

Abstract

Identifying adherence to direct oral anticoagulants (DOACs) plays a major role in treatment efficacy and safety. The DOAC Dipstick can detect DOACs in urine samples of acutely diseased patients at plasma thresholds of about 30 ng/mL. A prospective observational consecutive cohort study was performed on outpatients taking DOACs. The presence of direct oral factor Xa inhibitors (DXIs) in patient urine samples were independently evaluated by visual interpretation of the DOAC Dipstick pad colors. DOAC plasma concentration was assessed using STA®-Liquid Anti-Xa and STA®-Liquid Anti-IIa chromogenic substrate assays. Positive DOAC Dipstick results were compared with a threshold plasma of DOAC concentration ≥30 ng/mL. Of 120 patients (age 55.4 + 16.1 years, female n = 63), 77 were on rivaroxaban and 43 on apixaban. Plasma concentrations were 129 ± 118 ng/mL for rivaroxaban, and 163 ± 130 ng/mL for apixaban, DOAC Dipstick test has a sensitivity of 97.2% and a positive predictive value of 89.5% at 30 ng/mL. No differences occurred between DXIs. Specificity and negative predictive value could not be determined due to the low number of true negative values. There were no differences in the interpretation of rivaroxaban and apixaban pad colors between observers (Kappa 1.0). Results show that DOAC Dipstick may be a useful tool for identifying DXIs in urine samples in an outpatient setting at a plasma threshold ≥ 30 ng/mL. Further studies should include patients treated with dabigatran, vitamin K antagonists, or other anticoagulants.

Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper

“…2). 20,[22][23][24][25] All identified studies used 30 ng/mL as a clinically significant threshold. True positives (TPs) are defined as DOAC Dipstick positive with plasma DOAC concentration 30 ng/mL while true negatives (TNs) are defined as DOAC Dipstick negative with plasma concentrations <30 ng/mL.…”

“…DOAC concentrations were measured using either LC-MS/MS, representing the gold standard, 23 or a calibrated chromogenic assay. 20,22,24,25 A summation of the DOAC Dipstick performance characteristics for each study is provided in ►Table 2. Studies that included DOAC-naïve normal subjects (controls) were excluded in this analysis.…”

“…20 Study #4: A prospective observational cohort study of consecutively enrolled outpatients treated with apixaban (n ¼ 43) or rivaroxaban (n ¼ 77) for recurrent VTE. 24 Study #5: A single-center, prospective, two-armed observational study comprising an acute arm including 17 patients with nonvalvular AF and ischemic stroke with an indication for thrombolysis (apixaban n ¼ 11, rivaroxaban n ¼ 5, and dabigatran n ¼ 1) and a subacute arm including 24 AF patients on secondary prophylaxis for ischemic stroke (n ¼ 21 with apixaban, n ¼ 1 with rivaroxaban, n ¼ 2 with dabigatran). 25 The individual values of each study for TP and FP and for TN and FN results of the direct oral FXa and thrombin inhibitor pads of the dipstick are summarized in ►Table 1.…”

“…In four studies, 20,22,24,25 urine dipstick results were compared with plasma DOAC concentrations determined using DOAC-specific calibrated chromogenic anti-Xa assays and in one study, 23 plasma concentrations of FXa DOACs and of dabigatran (n ¼ 265 each) were determined by LC-MS/MS (►Table 2). In total, there were n ¼ 842 (n ¼ 577 plus n ¼ 265) evaluations of urine dipstick pads from all five studies.…”

“…The sub-analysis for rivaroxaban, apixaban (5 studies), 20,[22][23][24][25] and edoxaban (1 study) 23 showed a difference in their performance, with comparatively lower NPV for apixaban (81.8%) than for rivaroxaban (97.9%) or edoxaban (100%). The other statistical parameters ranged between 53 and 84% (►Supplementary Tables S1 and S2, available in the online version).…”