Georges Jourdi1, Maxime Delrue2, Alain Stepanian2, Jessica Valaize3, Geoffrey Foulon-Pinto4, Julien Demagny5, Jerome Duchemin6, Fabienne Nedelec-Gac3, Luc Darnige7, Emmanuel Curis8, Xavier Delavenne9, Pascale Gaussem7, Virginie Siguret4, Isabelle Gouin-Thibault10. 1. Université de Paris, U1140 Innovative Therapies in Haemostasis, INSERM, F-75006 Paris, France; Service d'Hématologie Biologique, AP-HP, Cochin Hospital, F-75014 Paris, France. Electronic address: georges.jourdi@aphp.fr. 2. University Institute of Hematology, EA 3518, Saint-Louis Hospital, Paris, France; Service d'Hématologie Biologique, AP-HP, Lariboisière Hospital, F-75010 Paris, France. 3. Service d'Hématologie Biologique, CHU Pontchaillou, Rennes, France. 4. Université de Paris, U1140 Innovative Therapies in Haemostasis, INSERM, F-75006 Paris, France; Service d'Hématologie Biologique, AP-HP, Lariboisière Hospital, F-75010 Paris, France. 5. Service d'Hématologie Biologique, AP-HP, Lariboisière Hospital, F-75010 Paris, France. 6. Service d'Hématologie Biologique, AP-HP, Cochin Hospital, F-75014 Paris, France. 7. Université de Paris, U1140 Innovative Therapies in Haemostasis, INSERM, F-75006 Paris, France; Service d'Hématologie Biologique, AP-HP, Georges Pompidou European Hospital, F-75015 Paris, France. 8. Laboratoire de biomathématiques EA 7537, Faculté de Pharmacie, Université de Paris, France; Service de biostatistiques et informatique médicale SBIM, Saint Louis Hospital, AP-HP, Paris, France. 9. University of Lyon, Inserm U1059, Saint-Etienne, France; Laboratory of Pharmacology and Toxicology, CHU Saint-Étienne, Saint-Étienne, France. 10. Service d'Hématologie Biologique, CHU Pontchaillou, Rennes, France; University of Rennes 1, CIC-Inserm1414, Rennes, France.
Abstract
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®.
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-DOACpatients 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 DOACpatients, 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®.