Measuring the activity of apixaban and rivaroxaban with rotational thrombelastometry

Adelmann, Dieter; Wiegele, Marion; Wohlgemuth, Rudolf Karl; Koch, Stefan; Frantal, Sophie; Quehenberger, Peter; Scharbert, Gisela; Kozek-Langenecker, S.; Schaden, Eva

doi:10.1016/j.thromres.2014.08.006

Cited by 66 publications

(72 citation statements)

References 20 publications

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“…7–10 In our study, all kinetic parameters of NATEM assay were significantly affected by the 2 drugs to a similar extent compared with controls. However, no statistically significant effect was detected on the final strength of the clot and the speed of fibrinolysis in both groups of patients, compared to controls.…”

Section: Discussionsupporting

confidence: 68%

Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation

Tsantes

Kyriakou²,

Ikonomidis³

et al. 2016

Medicine

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There is a shortage of data in everyday clinical practice about the anticoagulant effects caused by the new oral anticoagulants (NOAs). Our aim was to estimate the intensity of anticoagulant activity induced by rivaroxaban 20 mg qd and dabigatran 110 mg bid among patients with nonvalvular atrial fibrillation (NV-AF).We studied 20 patients with NV-AF treated with dabigatran, and 20 patients treated with rivaroxaban. We performed conventional coagulation tests, thrombin generation (TG) test, thromboelastometry (ROTEM), and epinephrine-induced light transmission aggregometry (LTA) in all 40 patients and 20 controls. Hemoclot Thrombin Inhibitors (HTI) and Factor Xa Direct Inhibitor (DiXaI) assay were used to measure dabigatran and rivaroxaban plasma levels, respectively.Measurements of all assays estimating anticoagulant activity across the 2 patient groups were similar, except for aPTT. Patients on dabigatran exhibited statistically significantly prolonged aPTT values (P < 0.001). In LTA, patients on dabigatran also showed decreased aggregation compared to those on rivaroxaban (P = 0.045). Regarding the TG test, there was no association between endogenous thrombin potential (ETP) and rivaroxaban plasma levels (P = 0.33) as opposed to dabigatran levels (P < 0.001), but significant correlations were observed between rivaroxaban plasma concentrations and kinetic parameters of TG assay (Tlag, P = 0.045; Tmax, P = 0.016; and Cmax, P = 0.003).Based on ROTEM and TG assays, the anticoagulant effects induced by the 2 drugs given in the specific dose regimens in real-world patients were comparable. Only platelet aggregation was found to be more affected by dabigatran as compared to rivaroxaban.

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Section: Discussionsupporting

confidence: 68%

Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation

Tsantes

Kyriakou²,

Ikonomidis³

et al. 2016

Medicine

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“…In contrast, the ROTEM test allows for rapid detection of coagulation abnormalities at the point of care since its results may be obtained within several minutes [13]. Until now, only a few reports have been published concerning the value of the ROTEM device in the context of rivaroxaban therapy [14][15][16]. However, none of these studies incorporated patients treated for VTE.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Adelmann et al [15] demonstrated that a modified ROTEM test (low-tissue factor activated ROTEM) is a very sensitive tool for rivaroxaban detection. The authors observed a strong correlation (r = 0.81) between CT and rivaroxaban plasma concentrations.…”

Section: Discussionmentioning

confidence: 99%

Effects of Rivaroxaban Therapy on ROTEM Coagulation Parameters in Patients with Venous Thromboembolism

Chojnowski¹,

Górski²,

Robak³

et al. 2015

Adv Clin Exp Med

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This is especially important, since, as with other new oral anticoagulants (NOACs), no specific antidote exists for the reversal of its anticoagulant effect in the case of severe bleeding [6].It has to be emphasized that no single laboratory hemostasis test has shown any direct correlation between rivaroxaban plasma levels and either anticoagulant efficacy or the risk of bleeding. Nevertheless, anti-FXa chromogenic assays seem to be better than prothrombin time (PT) assessment for the quantitative measurement of Xarelto plasma Rivaroxaban (Xarelto), a direct, specific Factor Xa (FXa) inhibitor, is nowadays broadly used for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, as well as the prevention and treatment of venous thromboembolism (VTE) in various clinical settings [1][2][3]. Although rivaroxaban does not require routine coagulation monitoring, measurement of its plasma concentration is highly recommended in certain situations, including overdoses, drug accumulation or during the period before urgent surgery [4,5]. AbstractBackground. Rivaroxaban (Xarelto) does not require routine coagulation monitoring; however, in certain clinical situations (overdose, drug accumulation, urgent surgery) measurement of its plasma concentration is highly recommended. Currently, there is no single hemostasis test that shows a direct correlation between rivaroxaban plasma levels and anticoagulant efficacy. Objectives. This study was intended to assess the value of ROTEM in determining rivaroxaban administration. Material and Methods. Thirteen patients with venous thromboembolism and 13 healthy volunteers were compared with regard to certain ROTEM parameters and anti-FXa activity. The tests were done before the administration of 20 mg rivaroxaban (i.e. 24 h after previous administration) and 2.5 h afterwards.Results. The study group demonstrated residual activity of rivaroxaban in plasma (20 ± 11.3 ng/mL) 24 h following the previous administration, which did not cause marked changes in clotting assays compared to controls. In the group, 2.5 h after rivaroxaban administration, prolongation of PT (PTratio 1.51 ± 0.22), APTT (APPTratio: 1.30 ± 0.14) and ROTEM CT (CTratio -EXTEM: 2.45 ± 1.06, CTratio -INTEM: 1.32 ± 0.21) were observed. The cut-off values for particular tests were created to determine if the patient had achieved desirable anticoagulant effect after rivaroxaban administration. The mean anti-FXa values were significantly lower in patients before rivaroxaban dosing than after. Conclusions. PT demonstrated better diagnostic value than APTT in rivaroxaban administration. The ROTEM clotting time (CT) according to EXTEM may be used to determine the anticoagulation effect of rivaroxaban, but is not sensitive enough to measure the residual activity of this drug (Adv Clin Exp Med 2015, 24, 6, 995-1000).

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“…In the whole blood TEM with standard reagents (EXTEM, INTEM), only the clotting time is affected to some extent [32]. When applying in a clinical setting, a modified whole blood TEG/TEM with very low TF or a TEG/TEM without TF or kaolin/celite seems more appropriate but this requires further validation [64,72,99]. Of importance is the notion that whole blood assays are affected by NOACs to a lesser extent than assays in platelet poor plasma.…”

Section: Introductionmentioning

confidence: 99%

Global assays and the management of oral anticoagulation

Brinkman

2015

Thrombosis Journal

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Coagulation tests range from global or overall tests to assays specific to individual clotting factors and their inhibitors. Whether a particular test is influenced by an oral anticoagulant depends on the principle of the test and the type of oral anticoagulant. Knowledge on coagulation tests applicable in monitoring status and reversal of oral anticoagulation is a prerequisite when studying potential reversal agents or when managing anticoagulation in a clinical setting. Specialty tests based on the measurement of residual activated factor X (Xa) or thrombin activity, e.g., are highly effective for determining the concentration of the new generation direct factor Xa- and thrombin inhibitors, but these tests are unsuitable for the assessment of anticoagulation reversal by non-specific prohemostatic agents like prothrombin complex concentrate (PCC) and recombinant factor VIIa (FVIIa). Global coagulation assays, in this respect, seem more appropriate. This review evaluates the current status on the applicability of the global coagulation assays PT, APTT, thrombin generation and thromboelastography in the management of oral anticoagulation by vitamin K antagonists and the direct factor Xa and thrombin inhibitors. Although all global tests are influenced by both types of anticoagulants, not all tests are useful for monitoring anticoagulation and reversal thereof. Many (pre)analytical conditions are of influence on the assay readout, including the oral anticoagulant itself, the concentration of assay reagents and the presence of other elements like platelets and blood cells. Assay standardization, therefore, remains an issue of importance.

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Measuring the activity of apixaban and rivaroxaban with rotational thrombelastometry

Cited by 66 publications

References 20 publications

Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation

Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation

Effects of Rivaroxaban Therapy on ROTEM Coagulation Parameters in Patients with Venous Thromboembolism

Global assays and the management of oral anticoagulation

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