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

Abstract

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).

Impact of four direct oral anticoagulants on rotational thromboelastometry (ROTEM)

“…Our results are in accordance with data previously published by Casutt et al who reported a slight increase in EXTEM CT and INTEM CT after a prophylactic dose of 10 mg rivaroxaban had been administered to healthy volunteers. Chojnowski et al reported the impact of administration of 20 mg rivaroxaban on INTEM, EXTEM and APTEM and found EXTEM CT more sensitive than INTEM CT, which is in line with our results. Adelmann et al studied the impact of in vitro spiking with apixaban and rivaroxaban on modified ROTEM tests (low tissue factor‐ROTEM and PiCT‐ROTEM) which would be more sensitive than the usually available ROTEM tests that had nevertheless not been directly compared.…”

The use of frozen plasma samples in thromboelastometry

“…The influence of dabigatran and rivaroxaban on viscoelastic properties of whole blood was demonstrated previously [ 17 , 40 ]. In plasma samples, the CT was further increased compared to whole blood.…”

Laboratory Assessment of Direct Oral Anticoagulants

“…108 However, using the EXTEM reagents, it has been reported as not sufficiently sensitive to assess the residual activity of rivaroxaban in patients. 107,109 With thrombin generation assays, there was a modest correlation (R ¼ 0.54) with dabigatran concentration and lag time, but paradoxical increases in the endogenous thrombin potential (ETP). 110 The paradoxical increase in ETP was also confirmed in orthopedic surgery patients taking daily doses of 150 or 220 mg dabigatran, as reported by Samama and colleagues.…”