Antithrombotic effect of two low molecular weight thrombin inhibitors and a low-molecular weight heparin in a caval vein thrombosis model in the rat

Thromb Haemost. 1997 Nov;78(5):1404-7.


A sensitive thrombosis model with a high reproducibility was developed in the rat, utilizing stasis of the caval vein and a standardized surgical trauma as the only thrombogenic stimuli. Since no procoagulant substances were used, the results of the present study might be relevant in a clinical situation. The antithrombotic effect of two recently synthesized low-molecular-weight thrombin inhibitors have been compared to dalteparin, (Fragmin) a low-molecular-weight heparin fragment. Each compound was studied at 8 different doses with 10 rats in each group. On a gravimetric basis, the thrombin inhibitor melagatran was twice as potent as dalteparin (ED50 16 and 33 microg/kg per h, respectively). The second thrombin inhibitor, inogatran, had an intermediate effect, with an ED50 of 24 microg/kg per h. No differences in antithrombotic effect were, however, found when the compounds were compared at anticoagulant equivalent doses (same APTT prolongation). A 50% reduction in the mean thrombus weight was obtained when APTT was prolonged to 1.2 to 1.3 times the pretreatment value.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Azetidines
  • Benzylamines
  • Dalteparin / therapeutic use
  • Disease Models, Animal
  • Fibrinolytic Agents / therapeutic use*
  • Glycine / analogs & derivatives
  • Glycine / therapeutic use
  • Heparin, Low-Molecular-Weight / pharmacology*
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Piperidines / therapeutic use
  • Rats
  • Rats, Wistar
  • Thrombin / antagonists & inhibitors*
  • Thrombophlebitis / drug therapy*
  • Vena Cava, Inferior*


  • Azetidines
  • Benzylamines
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Piperidines
  • melagatran
  • inogatran
  • Thrombin
  • Dalteparin
  • Glycine