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

G. Jourdi (1) , M. Delrue (2) , A. Stepanian (2) , J. Valaize (3) , G. Foulon-Pinto (1) , J. Demagny (4) , J. Duchemin (4) , F. Nedelec-Gac (3) , L. Darnige (1) , E. Curis (5) , X. Delavenne (6) , P. Gaussem (1) , V. Siguret (1) , I. Gouin-Thibault (7, 3)

1 IThEM - U1140 - Innovations thérapeutiques en hémostase
2 (EA_3518) - Recherche clinique appliquée à l'hématologie
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
4 Hôpital Raymond Poincaré [AP-HP]
5 BioSTM - EA 7537 - Biostatistique, traitement et modélisation des données biologiques
6 LBTO - Biologie Intégrative du Tissu Osseux
7 CIC - Centre d'Investigation Clinique [Rennes]

Introduction Lupus Anticoagulant 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 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®/Confirmation® (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 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 in 76, 85 and 95% of the patients, respectively. 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®. © 2019 Elsevier Ltd

Mots clés: Lupus anticoagulant; Dabigatran; Rivaroxaban; Apixaban; Antiphospholipid syndrome

Domaines: Hématologie

G. Jourdi, M. Delrue, A. Stepanian, J. Valaize, G. Foulon-Pinto, et al.. Potential usefulness of activated charcoal (DOAC remove®) for dRVVT testing in patients receiving Direct Oral AntiCoagulants. Thrombosis Research, 2019, 184, pp.86-91. ⟨10.1016/j.thromres.2019.11.001⟩. ⟨hal-02397750⟩