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Comparison of unfractionated heparin, low-molecular-weight heparin, low-dose and high-dose rivaroxaban in preventing thrombus formation on mechanical heart valves: results of an in vitro study

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Abstract

Thromboembolism and bleeding after mechanical heart valve replacement are still unsolved problems, particularly for patients requiring anticoagulative bridging therapy. The aim of this study was to investigate whether rivaroxaban, a new oral selective and direct coagulation factor Xa inhibitor, is as effective as enoxaparin and unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves using an in vitro system. Blood from healthy male donors was anticoagulated with either UFH, enoxaparin, rivaroxaban at 300 ng/ml, (n = 10 each), or rivaroxaban at 30 ng/ml (n = 3). Mechanical aortic valve prostheses were placed into the in vitro testing system THIA II and exposed to the anticoagulant blood mixtures at a pulsatile flow for 60 min. Overall thrombus weight, coagulation parameters, and electron microscopic features of thrombus formation on the valve surface were quantified as endpoints. The mean thrombus weights were 163 ± 64 mg for group 1 (UFH), 341 ± 63 mg for the group 2 (enoxaparin), 238 ± 83 mg for group 3 (rivaroxaban 300 ng/ml) and 1.739 ± 16 mg for group 4 (rivaroxaban 30 ng/ml). Whereas high-dosed rivaroxaban showed no significant differences compared to UFH or enoxaparin, low-dosed rivaroxaban generated a massive thrombus generation, thus differing significantly from all other treatment groups regarding the thrombus weight. We hypothesize that high-dose rivaroxaban is a competitive oral available alternative to UFH and LMWH’s, that might be a worthwhile alternative for patients in need of anticoagulative bridging therapy. Prospective studies have to evaluate if rivaroxaban might even overcome the limitations of OAC in patients after implantation of artificial heart valves.

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Acknowledgments

This study was funded by an unrestricted grant from BAYER-Schering® Pharma.

Conflicts of interest

Mrs. Elisabeth Perzborn is an employee of Bayer HealthCare®.

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Authors and Affiliations

  1. Department of Internal Medicine III, Martin Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle, Germany

    Anja Kaeberich, Iris Reindl, Uwe Raaz, Alexander Vogt, Michael Buerke, Karl Werdan & Axel Schlitt

  2. Department of Cardiovascular Medicine, Stanford University, Stanford, CA, USA

    Lars Maegdefessel

  3. Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany

    Torsten Linde & Ulrich Steinseifer

  4. Bayer Schering Pharma AG, Wuppertal, Germany

    Elisabeth Perzborn

  5. Central Institute of the German Federal Armed Forces, Koblenz, Germany

    Baerbel Hauroeder

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  1. Anja Kaeberich
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  2. Iris Reindl
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Correspondence to Axel Schlitt.

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Kaeberich, A., Reindl, I., Raaz, U. et al. Comparison of unfractionated heparin, low-molecular-weight heparin, low-dose and high-dose rivaroxaban in preventing thrombus formation on mechanical heart valves: results of an in vitro study. J Thromb Thrombolysis 32, 417–425 (2011). https://doi.org/10.1007/s11239-011-0621-6

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