Measurement of rivaroxaban concentrations demonstrates lack of clinical utility of a <scp>PT</scp>,<scp> dPT</scp> and <scp>APTT</scp> test in estimating levels

Thöm, Ina; Cameron, Gary; Robertson, D. S.; Watson, Henry G.

doi:10.1111/ijlh.12846

Cited by 11 publications

(11 citation statements)

References 27 publications

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“…Baglin et al (9) presented three main methodologies for rivaroxaban monitoring: activated partial thromboplastin time (APTT), prothrombin time (PT), and determination of plasma drug levels or drug concentration. Although they are easily available and cheap, APTT and PT assays are not ideal assays for rivaroxaban measurement due to a discreet variation compared to normal values and a high dependency on the reagent used (10 –13). As Thom et al (13) reported, these tests present high specificity but lack sensitivity.…”

Section: Introductionmentioning

confidence: 99%

“…Although they are easily available and cheap, APTT and PT assays are not ideal assays for rivaroxaban measurement due to a discreet variation compared to normal values and a high dependency on the reagent used (10 –13). As Thom et al (13) reported, these tests present high specificity but lack sensitivity. In another work, our group also demonstrated this characteristic (14).…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

Aranda

Derogis

Sanches

et al. 2019

Braz J Med Biol Res

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The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=−0.771, P<0.001), amplitude after 5 min (rho=−0.763, P<0.001), and amplitude after 10 min (rho=−0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

Aranda

Derogis

Sanches

et al. 2019

Braz J Med Biol Res

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“…Further work is needed to understand these issue more comprehensively in dogs. An alternative approach described in people is the use of dilute PT (dPT), which may create a more physiological in vitro environment compared to standard PT 26–28 . There are conflicting reports, however, regarding the suitability of dPT assays as a surrogate for RIVA in people 26,27 .…”

Section: Discussionmentioning

confidence: 99%

“…An alternative approach described in people is the use of dilute PT (dPT), which may create a more physiological in vitro environment compared to standard PT 26–28 . There are conflicting reports, however, regarding the suitability of dPT assays as a surrogate for RIVA in people 26,27 . Dilute PT has been investigated in healthy cats receiving rivaroxaban 29 but to the authors’ knowledge has not been examined in dogs.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of point‐of‐care coagulation tests as alternatives to anti‐Xa activity for monitoring the anticoagulant effects of rivaroxaban in healthy dogs

Lynch

Ruterbories

Griffith

et al. 2020

J Vet Emergen Crit Care

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Objective To evaluate a panel of coagulation assays for their potential utility in rivaroxaban monitoring as alternatives to the rivaroxaban‐specific anti‐Xa activity (RIVA). Design Prospective experimental study. Setting University research laboratory. Animals Five healthy neutered male Beagles. Interventions Dogs were administered a median dose of 1.8 mg/kg rivaroxaban (range, 1.6–1.8 mg/kg) orally once daily for 2 consecutive days as part of a pharmacodynamic study. Blood was collected from a preplaced jugular catheter at time points relative to their rivaroxaban administration (0, 2, 4, 8, 24, 36, and 48 h) for measurement of RIVA, prothrombin time (PT), activated partial thromboplastin time, RapidTEG, and thrombin generation variables. Measurements and main results One hundred forty data points were available for analysis. There was poor correlation between RIVA and RapidTEG variables: R time (R) (min) (r = 0.554, P < 0.0001), K time (K) (min) (r = –0.204, P = 0.016), alpha angle (degrees) (r = 0.152, P = 0.073), Maximum amplitude (MA) (mm) (r = 0.106, P = 0.215), and G value (G) (dynes/s) (r = 0.108, P = 0.205). A good correlation was noted between thrombin generation variables and RIVA: lag time (min) (r = 0.827, P < 0.0001), peak (nM) (r = –0.752, P < 0.0001), and endogenous thrombin potential (nM·min) (r = –0.762, P < 0.0001). There was an excellent correlation between PT and RIVA (r = 0.915, P < 0.0001) and a good correlation between activated partial thromboplastin time and RIVA (r = 0.772, P < 0 .0001). Conclusions Of all the coagulation tests investigated, the PT correlated best with RIVA. There is potential for PT being a convenient second‐line monitoring option in dogs receiving rivaroxaban, but further work is necessary to validate other PT assays. Thromboelastography performed with strong activators correlated poorly with anti‐Xa activity.

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“…The search strategy identified 9169 citations. After reviewing titles and abstracts, 16 articles [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] evaluating the performance of coagulation indices were included in the systematic review. Among them, five studies in total were included in the quantitive analysis for rivaroxaban and dabigatran [11][12][13][14]23].…”

Section: Study Identification and Selectionmentioning

confidence: 99%

Diagnostic performance of coagulation indices for direct oral anticoagulant concentration

Zhang

Liu

et al. 2020

Thrombosis Research

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Introduction: Different coagulation indices for direct oral anticoagulants (DOACs) exist in clinical practice, but limited data are available for the diagnostic power of these indices. This review and meta-analysis aims to explore the diagnostic value of coagulation indices for DOACs. Materials and methods: PubMed, Web of Science, EMBASE, Clinical Trials.gov, and the Cochrane Library were searched from inception of each database to 15 February 2020. Studies reporting a relationship between coagulation indices and the gold standard (liquid chromatography/tandem mass spectrometry) were included in the analysis. Results: Sixteen articles from 9169 citations evaluating the performance of coagulation indices were included in this review. A total of 236, 273, 273 rivaroxaban samples were included to assess the diagnostic power of anti-Xa activity (AXA), prothrombin time (PT), combined PT and activated partial thromboplastin time, respectively. A total of 268 dabigatran samples were included to assess the diagnostic performance of diluted thromboplastin time (dTT). AXA calibrated by rivaroxaban showed a sensitivity of 0.98 (95% confidence interval (CI): 0.91-0.99) and a specificity of 0.98 (95% CI: 0.94-0.99) at the threshold of 30 ng/mL. For dabigatran, the combined sensitivity of dTT was 0.76 (95% CI: 0.66-0.84) and combined specificity was 0.97 (95% CI: 0.92-0.99). Conclusions: DOAC-specific calibrated AXA was a good index to indicate concentration for rivaroxaban and apixaban. More studies on edoxaban and betrixaban are in need. Diluted TT, thrombin inhibitor assay, and ecarin-based assays were potential to measure dabigatran concentration. Due to the limited data, results should be validated in the future.

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Measurement of rivaroxaban concentrations demonstrates lack of clinical utility of a PT, dPT and APTT test in estimating levels

Cited by 11 publications

References 27 publications

Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

Diagnostic accuracy of thromboelastometry and its correlation with the HPLC-MS/MS quantification test

Evaluation of point‐of‐care coagulation tests as alternatives to anti‐Xa activity for monitoring the anticoagulant effects of rivaroxaban in healthy dogs

Diagnostic performance of coagulation indices for direct oral anticoagulant concentration

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