Simplified Method for Removing Direct Oral Anticoagulant Interference in Mechanical Coagulation Test Systems—A Proof of Concept

Abstract

Background: Direct oral anticoagulants (DOACs) cause unwanted interference in various hemostasis assays, including lupus anticoagulant (LA) testing, where false positive and false negative identification may occur. DOAC Stop (DS) is an activated charcoal (AC) product used to specifically and effectively adsorb DOACs from test plasma. This process normally requires plasma treatment, centrifugation and plasma separation prior to tests, but inexperienced operators may also inadvertently transfer residual AC particles, thereby potentially adversely affecting clot detection. Methods: We hypothesized that residual DS might not be problematic for mechanical clot detection. We therefore investigated the potential impact of DS and a new DS liquid (DS-L) product on clotting tests using a mechanical clot detection system. Varying concentrations of DS were added to normal and abnormal plasmas with and without DOAC presence. Clotting tests including PT, APTT and dRVVT were performed directly in the analyzer without plasma/DS centrifugation. Results: DS up to double the recommended treatment level had only minor effects on all test results, despite completely obscuring visibility in the plasma/reagent mix. This confirms that the centrifugation step may be able to be omitted when using mechanical detection systems. Conclusions: Should DS carryover into treated plasmas occur, this should not cause issues with testing performed on mechanical clot-sensing devices. Moreover, we hypothesize that DS can be used directly in these systems, without the need for centrifugation, thereby simplifying its many potential applications.

Testing for the lupus anticoagulant: the good, the bad, and the ugly

“…Despite differential assay variability in sensitivity to apixaban, the end result, in general, is a decrease in screen/confirm ratio, and thus potential for false negative LA in an LA-positive patient. For B, D, and E, the red horizontal dashed line at a ratio of 1.2 represents the “default” cutoff for positive/negative LA findings, as used by the majority of RCPAQAP participants [ 10 , [26] , [27] , [28] ]. The data reflects normal pool plasma spiked with various concentrations of the DOACs; as the DOAC concentration increases, a higher proportion of dRVVT screen and confirm test times exceed the cutoffs.…”

“…More recently, the manufacturer of DOAC-Stop has generated an enhancement to the process of DOAC neutralization with a product they have called DOAC-Stop Liquid. This product requires less time for dispersal into plasma and thus more quickly neutralizes DOACS (within 2 minutes in most cases, compared with 5 to 10 minutes for the standard product) [ 28 ]. This product was able to neutralize up to 2000 ng/mL of the assessed DOACS (apixaban, rivaroxaban, and dabigatran) in the assessed hemostasis assays [ 28 ].…”

“…This product requires less time for dispersal into plasma and thus more quickly neutralizes DOACS (within 2 minutes in most cases, compared with 5 to 10 minutes for the standard product) [ 28 ]. This product was able to neutralize up to 2000 ng/mL of the assessed DOACS (apixaban, rivaroxaban, and dabigatran) in the assessed hemostasis assays [ 28 ]. Moreover, there was no need to centrifuge the material from the solution in the evaluated mechanical clot detection device [ 28 ].…”

“…This product was able to neutralize up to 2000 ng/mL of the assessed DOACS (apixaban, rivaroxaban, and dabigatran) in the assessed hemostasis assays [ 28 ]. Moreover, there was no need to centrifuge the material from the solution in the evaluated mechanical clot detection device [ 28 ]. Although further evaluation and confirmation are needed, this may reduce the process from the current 10 to 15 minutes per sample to ∼5 minutes per sample for mechanical clot detection systems [ 28 ].…”