DOAC Dipstick Testing Can Reliably Exclude the Presence of Clinically Relevant DOAC Concentrations in Circulation

Abstract

In certain clinical situations, it is necessary to determine whether clinically relevant plasma levels of direct oral anticoagulants (DOACs) are present. We examined whether qualitative testing of DOACs in urine samples can exclude DOAC plasma concentrations of >30 ng/mL. This prospective single centre cohort study included consecutive patients treated with an oral direct factor Xa inhibitor (DXI) (apixaban, n=31, rivaroxaban, n=53) and direct thrombin inhibitor (DTI) (dabigatran, n=44). We aimed to define the negative predictive value (NPV) and other statistical parameters of detecting DXIs and DTIs by DOAC Dipstick at plasma concentrations of >30 ng/mL. We also determined the best-fit threshold plasma levels using chromogenic substrate assays by logistic regression analysis. Between July 2020 and July 2021, 128 eligible patients (mean age 66 years, 55 females) were included into the study. The NPVs and sensitivities for DXI and DTI of DOAC Dipstick were 100% at >30 ng/ml plasma, for specificities 6% and 21% and for positive predictive values 62% and 72%, respectively. All diagnostic statistical tests improved to values between 86% and 100% at best fitting plasma thresholds of >14 ng/mL for DXI and >19 ng/mL for DTI. Visual analysis using the DOAC Dipstick was 100% in agreement with that of the optoeletronic DOASENSE Reader for all three DOACs. DOAC Dipstick testing can reliably exclude the presence of DOACs in urine samples at best fitting thresholds of >14 and >19 ng/mL in plasma. The performance of the DOAC Dipstick at detecting lower DOAC concentrations in plasma requires confirmation.

Performance of a Qualitative Point-of-Care Strip Test to Detect DOAC Exposure at the Emergency Department: A Cohort-Type Cross-Sectional Diagnostic Accuracy Study

“…Specificity for the subgroups (values ranging from 77% to 94%) are therefore higher than for the overall factor Xa inhibitor group (68.6%) and in a comparable range to the literature. 5,15,17 In this study, sensitivity, NPV, and PPV of the total and subgroups of factor Xa inhibitors and all values for dabigatran are less affected by the imbalance in the number of patients treated with thrombin and factor Xa inhibitors.…”

“…Furthermore, in our study cohort of emergency patients, apixaban urine levels were three times lower on average than in a cohort of stable patients recruited from nonemergency departments of a Croatian University hospital, as recently reported by Margetić and colleagues. 17 The difference is probably explained by the substantial proportion of patients with impaired renal function in our study cohort and may have contributed to the number of false-negative DOAC Dipstick results with apixaban samples.…”

“…However, the number of dabigatran samples in the study cohort was low, and the finding may have limited validity but is comparable to previously published data. 17 The sensitivity of the factor Xa pad was likewise high across plasma thresholds. Yet, the wrongful administration of thrombolysis or withholding of antidote administration in 3% of patients due to false-negative pad results might not be acceptable.…”

“…We decided to sum the results of the factor Xa pad of patients with dabigatran ( n = 31) and with factor Xa inhibitor ( n = 234, Table 1 ) according to the literature and vice versa for the thrombin inhibitor pad ( n = 265, Table 3 ). 5 15 17 The same procedure was followed for the evaluations of the rivaroxaban, apixaban, and edoxaban subgroups. For the evaluations of the subgroups with rivaroxaban, apixaban, and edoxaban, we further decided to use the factor Xa inhibitor pad of the dabigatran patients, which resulted in a higher number of results in Supplementary Table S2 (available in the online version) by n = 31 compared with the patients in Table 2 who were actually treated with a factor Xa inhibitor.…”

Point-of-Care Assessment of Direct Oral Anticoagulation in Acute Ischemic Stroke: Protocol for a Prospective Observational Diagnostic Accuracy Study

“…45 Recent efforts have been made to detect DOAC in urine samples using DOAC Dipsticks. 46 However, potential correlations with the time of last bladder emptying and the patient's renal or liver function remain to be investigated. Furthermore, study design limitations encompass a low sample size of patients with known DOAC status limiting the application of study results as a screening tool in a real-life scenario where a urine sample is not readily available as well.…”