Journal of Thrombosis and Thrombolysis

, Volume 37, Issue 2, pp 118–130

In vitro comparison of the novel, dual-acting FIIa/FXa-inhibitor EP217609C101, unfractionated heparin, enoxaparin, and fondaparinux in preventing cardiac catheter thrombosis

  • Anja Kaeberich
  • Uwe Raaz
  • Alexander Vogt
  • Lars Maedgefessel
  • Eric Neuhart
  • Chantal Krezel
  • Ludovic Drouget
  • Baerbel Hauroeder
  • Michael Buerke
  • Karl Werdan
  • Axel Schlitt
Article

DOI: 10.1007/s11239-013-0938-4

Cite this article as:
Kaeberich, A., Raaz, U., Vogt, A. et al. J Thromb Thrombolysis (2014) 37: 118. doi:10.1007/s11239-013-0938-4

Abstract

Efficient and safe anticoagulation is crucial in patients requiring percutaneous coronary intervention (PCI) or extracorporeal circulation during cardiac surgery. Although new anticoagulant strategies have emerged for PCI as alternatives to the established treatment with heparins, the development of new anticoagulants with an improved efficacy/safety ratio is still necessary. Our study compared the efficacy of the novel, dual-acting, neutralizable FIIa/FXa-inhibitor EP217609C101 (EP) at 2, 1.2, 0.9, and 0.6 μg/ml to unfractionated heparin (UFH), enoxaparin, and fondaparinux in preventing cardiac catheter thrombosis under in vitro conditions. Blood drawn by venepunction from healthy male volunteers (n = 10) pretreated with 500 mg aspirin orally was treated with the anticoagulant to test and continuously circulated through a cardiac catheter for 60 min or until the catheter became blocked by thrombotic debris. Anticoagulant efficacy was assessed by thrombus weight, electron microscopic features of the developing thrombi, and laboratory parameters. Whereas UFH, enoxaparin, EP 2, and EP 1.2 μg/ml secured maximum circulation times, statistically significant premature catheter occlusions were observed for EP 0.9, EP 0.6 μg/ml, and fondaparinux. The UFH group and both high-dose concentrations of EP showed significantly lower thrombus weights than the low-dose concentrations of EP and fondaparinux, (p ≤ 0.05). On electron microscopic analysis of the thrombotic debris no differences were observed in erythrocyte deposition between UFH, enoxaparin, and all EP concentrations tested. A significant reduction in fibrin deposition was achieved by UFH and EP 2 μg/ml but no significant differences in platelet deposition were found, except for a significant reduction for EP 0.6 μg/ml. Our in vitro study showed that EP217609C101 is a promising new drug that is dose-dependently superior to classical (UFH, enoxaparin) and newer (fondaparinux) drugs in preventing heart catheter thrombosis.

Keywords

New anticoagulants Coronary heart disease Percutaneous coronary intervention Heart catheter thrombosis 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Anja Kaeberich
    • 1
  • Uwe Raaz
    • 1
    • 2
  • Alexander Vogt
    • 1
  • Lars Maedgefessel
    • 3
  • Eric Neuhart
    • 4
  • Chantal Krezel
    • 4
  • Ludovic Drouget
    • 5
  • Baerbel Hauroeder
    • 6
  • Michael Buerke
    • 1
    • 7
  • Karl Werdan
    • 1
  • Axel Schlitt
    • 1
    • 8
  1. 1.Department of Internal Medicine IIIMartin-Luther-University Halle-WittenbergHalleGermany
  2. 2.Department of Cardiovascular MedicineStanford UniversityStanfordUSA
  3. 3.Karolinska InstituteStockholmSweden
  4. 4.Endotis Pharma, Parc BiotechRomainvilleFrance
  5. 5.Laboratoire de Thrombose et d’AthéroscléroseHôpital LariboisièreParisFrance
  6. 6.Central Institute of the Federal Armed ForcesKoblenzGermany
  7. 7.Department for Cardiology and AngiologySt. Marien-HospitalSiegenGermany
  8. 8.Department of CardiologyParacelsus-Harz-Clinic Bad SuderodeQuedlinburgGermany

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