The Influence of Assay Selection on Prothrombin Time Measured in Patients Treated With Rivaroxaban for Nonvalvular Atrial Fibrillation

Shimomura, Daiki; Nakagawa, Yoshihisa; Kondo, Hirokazu; Tamura, Toshihiro; Amano, Masashi; Enomoto, Soichiro; Onishi, Nobuyuki; Tamaki, Yodo; Miyake, Makoto; Kaitani, Kazuaki; Izumi, Chisato; Fukuda, Aya; Nakamura, Fumihiko

doi:10.1002/jcla.21960

Cited by 7 publications

(7 citation statements)

References 17 publications

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“…However, PT does not always predictably reflect the anticoagulant activity of rivaroxaban, and the sensitivity of PT to rivaroxaban depends on the laboratory reagents used. 16,27,28 APTT was less sensitive to apixaban and rivaroxaban than PT, which concurs with previous reports. 24,25 In the present study, APTT was well correlated with plasma rivaroxaban levels in patients treated with rivaroxaban ( Table 4).…”

Section: Discussionsupporting

confidence: 90%

“…Only PT (%) results were well correlated with plasma apixaban levels, whereas both PT (sec) and PT (%) results were well correlated with plasma rivaroxaban levels. However, PT does not always predictably reflect the anticoagulant activity of rivaroxaban, and the sensitivity of PT to rivaroxaban depends on the laboratory reagents used . APTT was less sensitive to apixaban and rivaroxaban than PT, which concurs with previous reports .…”

Section: Discussionsupporting

confidence: 89%

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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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: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

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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“…Although the correlation between PT and plasma concentration of rivaroxaban is known to vary depending on the reagents used for the PT test, 30,31 Thromborel S, which was used in this study, is known to correlate well with the plasma concentration of rivaroxaban estimated by anti-FXa activity assays within the therapeutic range. 32 Kubitza et al reported that renal clearance and total body clearance of rivaroxaban are decreased in patients with increasing renal impairment, leading to increased plasma concentrations, increased inhibition of FXa activity and prolongation of PT. 25 Our results are consistent with the findings of this previous study.…”

Section: Discussionmentioning

confidence: 99%

Impact of gene polymorphisms in drug‐metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation

Nakagawa

Kinjo

Iizuka

et al. 2020

Basic Clin Pharma Tox

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Direct oral anticoagulants (DOACs) are increasingly used in clinical practice to prevent venous thrombosis or thrombus formation in non-valvular atrial fibrillation (NVAF). 1 The usage of rivaroxaban, a factor Xa (FXa) inhibitor, increased from 0.13% to 13.87% from 2011 to 2014 in the United States of America (USA). 2 Rivaroxaban has been shown to have efficacy similar to that of warfarin for prevention of stroke or systemic embolism in patients with NVAF. 3 In addition, fatal bleeding and intracranial haemorrhage occur less frequently in patients receiving rivaroxaban than in those receiving warfarin. 3 Although DOACs do not require routine coagulation monitoring, serious bleeding events have been occasionally reported in patients taking these drugs. 4 Rivaroxaban was among the top 10 drugs involved in emergency department visits for adverse drug events in the United States in 2013-2014. 5 In addition, interindividual variability of the pharmacokinetics of rivaroxaban in patients with NVAF has been shown to be large. 6-9

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“… 12 , 17 Thus, physicians should reevaluate the PT agents that are used in their facilities and must be aware of the individual characteristics of the PT prolongation for each DOAC. 18 …”

Section: Discussionmentioning

confidence: 99%

Real-world monitoring of direct oral anticoagulants in clinic and hospitalization settings

Takatsuki

Kimura

Sugimoto³

et al. 2017

SAGE Open Medicine

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Background:The monitoring of the effects of direct oral anticoagulants may be beneficial during emergencies and adverse events. We aimed to explore direct oral anticoagulant monitoring in “real-world” settings, in which monitoring methods are limited and loading time can be estimated based on only patient reports.Methods:In 164 patients, plasma anti-Xa activity was assessed using a STA®-Liquid Anti-Xa reagent (Diagnostica Stago, Asnieres, France), and prothrombin time was measured using HemosIL® RecombiPlasTin 2G (Instrumentation Laboratory, Bedford, MA, USA). The loading time was calculated according to the previous dosing time reported by the patient. In the clinic setting, rivaroxaban and apixaban were administered to 103 patients with atrial fibrillation and a blood sample was tested once during a clinic visit. In the hospitalization setting, edoxaban was administered to 61 patients undergoing arthroplasty for prophylaxis of a venous thrombosis and blood samples were tested 3 and 18 h after the last intake.Results:Plasma Xa activity in the clinical setting ranged widely (rivaroxaban: 1.1–424.4 ng/mL, apixaban: 15.4–469.2 ng/mL) during the 11.7 ± 7.0 h following the previous dose. The values varied over a wide range (up to a factor of 2) at the same loading time, especially around the peak period. The plasma anti-Xa activity of rivaroxaban and apixaban showed linear correlations with prothrombin time (R2 = 0.828 and 0.717, respectively). Edoxaban administration prolonged the prothrombin time by only 1.6 ± 1.1 s from the trough to the peak, to a degree that was negatively correlated with age, but not with plasma creatinine level, creatinine clearance, or body mass index.Conclusion:In real-world settings, plasma anti-Xa monitoring should be interpreted considering the wide variations in data, reflecting the variability in patient-reported loading time and interpatient variability.

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The Influence of Assay Selection on Prothrombin Time Measured in Patients Treated With Rivaroxaban for Nonvalvular Atrial Fibrillation

Abstract: The estimated concentration of rivaroxaban varied greatly depending on the assay, so the PT measured in patients taking rivaroxaban should be interpreted with caution.

Cited by 7 publications

References 17 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

Impact of gene polymorphisms in drug‐metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation

Real-world monitoring of direct oral anticoagulants in clinic and hospitalization settings

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