In vivo and ex vivo effect of various rivaroxaban concentrations on thrombin generation

Bertaggia Calderara, Debora; Kröll, Dino; Gerschheimer, Christiane; Nicolas, Nicole; Stirnimann, Guido; Alberio, Lorenzo (May 2016). In vivo and ex vivo effect of various rivaroxaban concentrations on thrombin generation (Unpublished). In: ISTH 2016. Montpellier France. 05/2016.

used for treatment and prevention of venous thromboembolic events. An unsolved question is the anticoagulant efficacy of a given RVX concentration and its potential hemorrhagic risk related to surgical or pharmacological interventions. Aims: To assess the in vivo anticoagulant effect of various RVX concentrations. Methods: Blood samples from 12 obese patients receiving a single dose of 10 mg RVX before bariatric surgery were obtained at baseline and at different time points over 24 hrs. The anticoagulant effect was assessed in vivo, by monitoring thrombin-antithrombin complexes (TAT) and prothrombin fragments 1 + 2 (F1 + 2), and ex vivo by measuring tissue factor induced thrombin generation (TG) by calibrated automated thrombogram in patients’ platelets poor plasma. Results: Ex vivo: The highest inhibition of TG (>70%) was observed at Cmax (120 ng/ml) and it stayed at a similar level at RVX concentrations of 80–90 ng/mL. The degree of ex vivo TG inhibition declined to 50–60% with RVX concentrations of 50–60 ng/mL, to 30-35% at RVX 30 ng/mL, and to 15–18% at RVX 15 ng/ml. In vivo: TAT and F1-2 values significantly decreased at Cmax. During RVX plateau (80–90 ng/mL), a further significant decrease for both activation markers was observed. The anticoagulant effect reached a steady state at drug concentrations of 60–50 ng/mL. TAT and F1 + 2 increased when RVX concentration dropped below 50 ng/mL. Conclusions: The pattern of ex vivo inhibition of TG by RVX significantly differs between concentrations of 80–120 ng/ml, 50–60 ng/mL, 30 ng/mL, and 15 ng/mL. TG is progressively inhibited in vivo by steady-state RVX concentrations of 80–90 ng/mL. This is no longer the case when RVX falls below 60 ng/ml. Of note, at 30 ng/ml RVX is still able to inhibit TG ex vivo but not in vivo. These data show that ex vivo TG inhibition does not correlate with the in vivo effect and they contribute to define the in vivo anticoagulant efficacy of a given plasmatic RVX concentration.

Item Type:

Conference or Workshop Item (Poster)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Kröll, Dino and Stirnimann, Guido

Subjects:

600 Technology > 610 Medicine & health

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

15 May 2017 10:28

Last Modified:

19 Jun 2017 09:00

URI:

https://boris.unibe.ch/id/eprint/95845

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