The effect of DOACs on laboratory tests and their removal by activated carbon to limit interference in functional assays

Abstract

We aimed to review the interfering effect of DOACs on tests for haemostatic function and then to discuss overcoming these with activated carbon (AC) products, thereby eliminating DOAC issues from test plasmas. Recent relevant articles were reviewed and are discussed. Laboratory tests for DOACs, lupus anticoagulant, factor assays and APC Resistance were carried out in such publications with and without an AC product on various instruments using reagents approved for diagnostic use in well‐regulated clinical laboratories. All reports on this plasma pre‐treatment by AC products agree that they extract DOACs from plasma samples with minimal effect on underlying clotting tests. The specific extraction of DOACs significantly reduced false positive lupus anticoagulant detection and provided more reliable results in clotting factor assays, APC resistance and other thrombophilia tests. Dabigatran and edoxaban seem to be adsorbed more thoroughly by AC from plasmas than rivaroxaban and apixaban. In summary, most of the AC products reviewed here appear to remove DOACs from test plasmas without significantly affecting underlying clotting tests and permit correct diagnosis of various haemostatic conditions despite the initial presence of DOACs. The application of such agents as a sample pre‐treatment to overcome the effects of DOACs for routine coagulation testing is supported by the emerging literature.

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

“…38 Alternatively, in vitro removal of DOAC compounds from plasma prior to coagulation testing has been reported and may be more suitable. [39][40][41][42][43][44][45][46][47] DOAC-Stop (adsorbing agent, Hematex Research, Hornsby, Australia) and DOAC-Remove (activated carbon, 5-Diagnostics, Basel, Switzerland), both reportedly able to neutralize all DOACs with minimal effect on haemostasis tests, have been recently commercialized. [39][40][41][42][43][44][45][46][47] However, care should be taken, especially in LA testing, since in the reported studies, complete reversal did not occur in every sample and reversal varies among the different DOACs.…”

Is Lupus Anticoagulant a Significant Feature of COVID-19? A Critical Appraisal of the Literature

“…For heparin, mixing would reduce the effect on the aPTT and SCT, and possibly correct any effect on the dRVVT, should the dilution then lead to a heparin level within a therapeutic range (or generally <1 U/mL). For DOACs, one could use DOAC neutralizers such as DOAC Stop or DOAC Remove, 34 although this in itself may have an unexpected effect on LA detection. Irrespective, laboratories would need to apply such strategies to mitigate the effect of any anticoagulant and ensure appropriate detection of LA.…”

Review of coagulation preanalytical variables with update on the effect of direct oral anticoagulants

“…44 The use of activated charcoal has been demonstrated to be an effective means of neutralizing most DOACs to near nonmeasurable levels. 45,46 However, there is some concern that not all DOAC may be removed using this platform and post-charcoal measurement of DOAC concentration should be considered 45 as even the presence of small amounts of these drugs may have significant impacts on Dilute Russell's Viper Venom Time (DRVVT) testing and result interpretation (false positive). 19 Alternatively, some evidence exists for using DOAC insensitive reagents to more reliably assess for lupus anticoagulants, 47 but such platforms may not be readily available for clinical use.…”

“…Comparison of commercially available direct oral anticoagulants (DOAC) neutralizing products46,47,[49][50][51][52] …”