An optimized dRVVT-based assay to estimate the intensity of anticoagulation in patients treated with direct oral anticoagulants

Sennesael, Anne-Laure; Exner, Thomas; Châtelain, Bernard; Lessire, Sarah; Larock, Anne-Sophie; Vancraeynest, Christelle; Pochet, Lionel; Dogné, Jean‐Michel; Spinewine, Anne; Mullier, François; Douxfils, Jonathan

doi:10.1016/j.thromres.2017.06.034

Cited by 16 publications

(16 citation statements)

References 29 publications

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“…This assay uses a modified phospholipid-rich, liquid-stable, ready-to-use dRVVT reagent. 34 This study has limitations that deserve mention. Patients were not randomized to receive either apixaban or rivaroxaban because physicians decided on the drugs administered.Patients who received lower dosages were older and had lower creatinine clearance rates than patients who treated with higher dosages.…”

Section: Discussionmentioning

confidence: 92%

“…Recently, the DRVV‐DOAC assay was developed by Haematex Reserach TM . This assay uses a modified phospholipid‐rich, liquid‐stable, ready‐to‐use dRVVT reagent . Sennesael et al reported that DRVV‐DOAC results correlated well with plasma concentrations of apixaban, rivaroxaban, and dabigatran .…”

Section: Discussionmentioning

confidence: 99%

“…This assay uses a modified phospholipid‐rich, liquid‐stable, ready‐to‐use dRVVT reagent . Sennesael et al reported that DRVV‐DOAC results correlated well with plasma concentrations of apixaban, rivaroxaban, and dabigatran . Therefore, the dRVVT confirm test could be useful conventional coagulation assay for monitoring the plasma DOAC concentrations in negative lupus anticoagulation patients even if further studies with more samples and variant reagents are conducted.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of global laboratory methods and establishing on‐therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution

Park¹,

Seo

Park

et al. 2019

Clinical Laboratory Analysis

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BackgroundApixaban and rivaroxaban are approved for the prevention and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and embolic stroke in atrial fibrillation (AF) patients. The aim of this study was to find appropriate methods of monitoring the anticoagulant effects of are direct oral anticoagulants (DOACs) and establish on‐therapy ranges using conventional tests.MethodsA total of 184 samples were collected from 91 patients receiving DOACs. Concentrations of apixaban and rivaroxaban in plasma were accessed by an anti‐factor Xa chromogenic assay. PT, APTT, antithrombin, D‐dimer, dRVVT screen/confirm, FDP, and fibrinogen levels were measured. On‐therapy ranges were calculated by substituting previously reported trough plasma concentrations of DOACs.ResultsAnti‐factor Xa chromogenic assay‐based DOACs levels were 26.0‐279.5 (115.9 ± 56.5) ng/mL for apixaban at 2.5 mg BID, 19.9‐565.1 (205.3 ± 162.4) ng/mL for apixaban at 5 mg BID, 2.3‐395.3 (205.3 ± 162.4) ng/mL for rivaroxaban at 15 mg OD, 3.6‐494.8 (119.6 ± 95.1) ng/mL for rivaroxaban at 20 mg OD, and 9.6‐431.4 (140.8 ± 113.6) ng/mL for rivaroxaban at 15 mg BID. PT (%), antithrombin, and dRVVT confirm tests showed good correlation with plasma apixaban levels. Plasma rivaroxaban concentrations were correlated well with PT (sec), PT (%),and dRVVT confirm results. On‐therapy ranges established for dRVVT confirm test by linear regression were as follows: 1.32‐1.52 for apixaban 2.5 mg BID, 1.12‐1.75 for apixaban 5 mg BID, 1.11‐1.78 for rivaroxaban 15 mg OD, 1.09‐1.64 for rivaroxaban 20 mg OD, and 1.22‐1.81 for rivaroxaban 20 mg BID.ConclusionsApixaban concentrations were well correlated with PT (%), antithrombin, and dRVVT confirm test. Rivaroxaban concentrations showed good correlation with PT (sec), PT (%), and dRVVT confirm test.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of global laboratory methods and establishing on‐therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution

Park¹,

Seo

Park

et al. 2019

Clinical Laboratory Analysis

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“…Sennesael and colleagues recently reported on the use of an optimised DRVVT assay for the detection of DOACs, with the advantage that it was liquid-stabilised and therefore does not require additional time for reconstitution. 15 There are other potential tests that may be used in a similar way as screening tests for the presence of DOACs. Letertre and colleagues evaluated a diluted prothrombin time with factor II-and X-deficient plasma ("dFiixPT") for the detection of anticoagulants.…”

Section: Discussionmentioning

confidence: 99%

Screening test for direct oral anticoagulants with the dilute Russell viper venom time

Pratt¹,

Crispin

2018

European J of Haematology

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“…The amount of rivaroxaban extracted from the cell pellet was quantified by LC-MS/MS analysis according to a previously described method, with minor adaptive changes in the sample preparation 30 . The chromatography system was made up of an UPLC Acquity H-Class system (Waters) coupled with a tandem-quadrupole mass spectrometer Xevo TQ-S (Waters).…”

Section: Methodsmentioning

confidence: 99%

Effect of ABCB1 genetic polymorphisms on the transport of rivaroxaban in HEK293 recombinant cell lines

Sennesael

Panin²,

Vancraeynest

et al. 2018

Sci Rep

Self Cite

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Direct oral anticoagulants (DOAC) are substrates for the ABCB1 transporter (also called P-glycoprotein), an active efflux pump. ABCB1 polymorphisms have been previously reported to influence the pharmacokinetics of several drugs such as immunosuppressants and tyrosine kinase inhibitors. Recently, in vivo studies have suggested that genetic variants might contribute to the inter-individual variability in DOAC plasma concentrations. Therefore, we evaluated the in vitro effect of the most common coding ABCB1 single nucleotide polymorphisms (SNP), 1236 C > T-2677G > T-3435C > T, and the coding ABCB1 1199 G > A SNP on the transport activity towards rivaroxaban. HEK293 cells were transfected to overexpress the ABCB1 wild-type (1236C-2677G-3435C, 1199 G) or variant proteins (1236C-2677G-3435T, 1236T-2677T-3435T or 1199 A). ABCB1 expression decreased the intracellular accumulation of rivaroxaban, when compared to control cells. This confirms the involvement of ABCB1 in the active transport of rivaroxaban. However, the ABCB1 1236 C > T-2677G > T-3435C > T and 1199 G > A SNPs had no significant influence on the intracellular accumulation of rivaroxaban when compared to the wild-type protein. These results suggest that the ABCB1 coding SNPs investigated in the present study are unlikely to contribute to the inter-individual variability in rivaroxaban plasma concentrations.

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An optimized dRVVT-based assay to estimate the intensity of anticoagulation in patients treated with direct oral anticoagulants

Cited by 16 publications

References 29 publications

Evaluation of global laboratory methods and establishing on‐therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution

Evaluation of global laboratory methods and establishing on‐therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution

Screening test for direct oral anticoagulants with the dilute Russell viper venom time

Effect of ABCB1 genetic polymorphisms on the transport of rivaroxaban in HEK293 recombinant cell lines

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