Potential usefulness of activated charcoal (DOAC remove®) for dRVVT testing in patients receiving Direct Oral AntiCoagulants

Abstract

Introduction: Lupus Anticoagulant (LA) testing using dilute Russell Viper Venom Time (dRVVT) is challenging in patients receiving Direct Oral AntiCoagulants (DOAC) due to potential false positive results. In a multicenter study, we evaluated the in vitro removal of DOAC by activated charcoal (DOAC remove ®), allowing reliable dRVVT testing. Materials and Methods: Patient samples were analyzed before and after treatment with DOAC remove ® : 49 apixaban, 48 rivaroxaban, 24 dabigatran and 30 none. DOAC plasma concentrations were measured using anti-Xa or anti-IIa diluted thrombin time assays. In a subset of 28 samples, DOAC concentrations were also measured using HPLC-MS/MS following treatment with DOAC remove ®. DRVVT was performed using STA-Staclot dRVVT Screen ® /Confirm ® (Stago) or LAC-Screening ® /Confirm ® (Siemens). Results: Baseline median [min-max] concentrations were 94 [<20-479] for apixaban, 107 [<20-501] for rivaroxaban and 135 ng/mL [<20-792] for dabigatran; dRVVT screen ratio /confirm normalized ratio was positive in 47, 90 and 42 % of apixaban, rivaroxaban and dabigatran samples. Treatment with DOAC remove ® did not affect dRVVT results in non-DOAC patients while it resulted in DOAC concentrations < 20 ng/mL in 82, 98 and 100 % of samples, respectively. Concentrations were < 5 ng/mL with HPLC-MS/MS in 5 out of 10, 8 out of 10 and 7 out of 8 samples, respectively. DOAC remove ® corrected DOAC interference with dRVVT assays allowed excluding LA in 76, 85 and 95 % of the patients, respectively. without affecting dRVVT results in non-DOAC patients. Conclusion: For dRVVT testing in DOAC patients, we suggest the use of DOAC remove ® for every rivaroxaban sample, whereas it might only be used in positive apixaban and dabigatran samples. A residual DOAC interference cannot be ruled out in case of persisting dRVVT positive results after treatment with DOAC remove ®. For those with persisting positive results, LA-diagnosis using dRVVT remains questionable.

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

“…A particular version in mini‐tablet form was developed for more convenient application to 1ml volumes of test plasmas (DOAC Stop™, Haematex). Several studies have now been published which confirm that it and similar products (DOAC Remove) may be useful in blood coagulation testing labs to eliminate the in vitro effect of DOACs 6‐16 ; especially in testing for lupus anticoagulant.…”

“…The low phospholipid LA screen tests are not specific just for LA and are similarly prolonged by DOACs 19,20 . Abnormal LA screen results are obtained on most DOAC patient plasmas 7,10,13,14,30 . The dRVVT screen/confirm ratio is less affected but with higher levels of rivaroxaban (and to a lesser extent dabigatran) these can be above the usual cutoff.…”

“…Jourdi et al 14 carried out a multi‐centre evaluation of DOAC Remove™ in 121 DOAC patients. The AC corrected DOAC interferences with dRVVT assays in 76%, 85% and 95% of apixaban, rivaroxaban and dabigatran patients respectively.…”

Escaping the catch 22 of lupus anticoagulant testing

“…The last option is to test patients on anticoagulant treatment. However, it has emerged, that a high rate of false results in LAC-testing is observed with all DOACs and thrombin inhibitors, especially seen in samples with rivaroxaban 12–17. Most in vitro studies found that LAC results become false-positive.…”

“…When using DOAC-STOP, the results from patients in DOACs can be interpreted 15 19 22–24. A simple charcoal product (DOAC-Remove, 5-Diagnostics, Basel, Switzerland) may offer an alternative solution to eliminate anticoagulation effects before LAC testing 16 25. Another strategy would be to add specific reversal agents pre-analytically.…”