Expert consensus on an algorithm for rapid exclusion of clinically relevant plasma levels of direct oral anticoagulants in patients using the DOAC Dipstick

Introduction With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Some position papers have suggested measuring DOAC levels in patients presenting to emergency departments with serious bleeding, acute ischemic stroke or when major surgical interventions or other invasive procedures associated with high bleeding risk are needed. The levels must be determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) or with specialized assays, such as calibrated chromogenic assays or viscoelastic methods. Specific threshold blood levels, which vary from≤20 ng/mL to≤100 ng/mL, have been proposed to guide medical decision for patients taking dabigatran or direct oral factor Xa (FXa) inhibitors. DOAC Dipstick (DOASENSE^TM, Heidelberg, Germany) is a point-of-care test that uses a disposable test strip to detect DOACs in urine and to differentiate between dabigatran and direct oral FXa inhibitors.

Method A systematic literature search was performed between 1993 and June 2023 to identify relevant studies in PubMed (MEDLINE) and Cochrane Library databases. Inclusion criteria were the determination of DOACs in urine samples of patients with atrial fibrillation and venous thromboembolism with rivaroxaban, apixaban, edoxaban and dabigatran compared to LC-MS/MS or calibrated chromogenic assay and reporting a plasma threshold of≥30 ng/mL. Data were analyzed by simple pooling to determine DOAC Dipstick’s sensitivity, negative predictive value (NPV), positive predictive value (PPV) and specificity. Unweighted mean values of these statistics with 95% confidence intervals (CI) were calculated using Stata 17.0 confirmed by SAS version 4.5.

Results Of 1206 eligible studies, 5 clinical studies were eligible for inclusion in the pooled analysis. The sensitivity was>97%, (lower 95% CI>90%) for both DOAC classes. The NPV value for the direct oral FXa inhibitors was 86.6% (95% CI: 76%– 93.7%) and for dabigatran>99% (95% CI: 98% – 100%). The NPV for the DOAC Dipstick was similar to the PPV for factor Xa inhibitors and more robust for thrombin inhibitors confirming the primary utility of a negative urine DOAC Dipstick pad result is to identify clinically relevant DOAC concentrations at a threshold of≥30 ng/mL in the blood.

Conclusion Pooled analysis of five available studies, comparing DOAC Dipstick with LC-MS/MS or DOAC-calibrated chromogenic assays indicates an acceptably high negative predictive value for exclusion of DOACs requiring verification of a match with the patient's clinical picture. The DOAC Dipstick excludes clinically relevant blood concentrations of DOACs at a threshold of≥30 ng/mL, which may support clinical decision-making in critical medical situations, such as excessive bleeding, prior to intravenous thrombolysis, or before urgent surgical procedures.

Publication History

Article published online:
26 February 2024