In vitro detection and removal of direct oral anticoagulants from patient plasma specimens

Abstract

: Medical laboratory scientists are often called upon to detect and identify the presence of direct oral anticoagulants in patient plasma, especially in emergent circumstances. Clot-based or chromogenic laboratory assays are often required to detect coagulopathies, coagulation factor inhibitors, or lupus anticoagulants (LA) but are limited by the presence of therapeutic anticoagulants that may invalidate the accuracy of the assay by falsely prolonging clot-based assay intervals and raising chromogenic assay results. We describe a semiquantitative urine reagent strip, DOAC-Dipstick® that may be employed to detect all direct oral anticoagulants and distinguish oral direct thrombin inhibitors (DTI) from oral anti-activated factor X (Xa) inhibitors. A limit of 30 ng/mL was established as the threshold for positivity using the strips. For oral anti-activated factor X inhibitors, the strips’ false positive rate was 4% and false negative rate was 2%. For the oral DTI, the strips’ false positive rate was 0.5% and false negative rate was 0.6%. We further describe four similar devices, DOAC-Stop®, DOAC-Remove®, DP-Filter® and DOAC Filter®, designed to remove direct anticoagulants from plasma by adsorption, filtration and precipitation, while essentially leaving intact native procoagulants suitable for testing. These devices employ activated charcoal (carbon) or similar formulations for adsorption. In LA testing, the DOAC-Stop® device reduces the initial PTT-LA interval for all DOACs by a mean of 21 seconds; there is no reduction for specimens with apixaban, 20 seconds for rivaroxaban, and 25.9 seconds for dabigatran. For the DRVVT assay, DOAC-Stop® removed the anticoagulants from 35 out of 41 specimens. By judiciously selecting and applying these devices and observing their limitations, laboratories may report clot-based and chromogenic substrate results, as alternately affected by DOAC presence, with reasonable confidence.