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Thromb Haemost 1997; 78(05): 1404-1407
DOI: 10.1055/s-0038-1665419
Review Article
Schattauer GmbH Stuttgart

Antithrombotic Effect of Two Low Molecular Weight Thrombin Inhibitors and a Low-Molecular Weight Heparin in a Caval Vein Thrombosis Model in the Rat

B I Eriksson
1   The Department of Orthopaedics, Sahlgrenska University Hospital, Astra Hässle AB
,
S Carlsson
3   Preclinical Research and Development, University of Göteborg, Astra Hässle AB
,
M Halvarsson
2   The Department of Surgery, Sahlgrenska University Hospital, Astra Hässle AB
,
B Risberg
2   The Department of Surgery, Sahlgrenska University Hospital, Astra Hässle AB
,
C Mattsson
3   Preclinical Research and Development, University of Göteborg, Astra Hässle AB
› Author Affiliations
Further Information

Publication History

Received 21 1997

Accepted after resubmission 26 June 1997

Publication Date:
12 July 2018 (online)

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Summary

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 µ/kg per h, respectively). The second thrombin inhibitor, inogatran, had an intermediate effect, with an ED50 of 24 µLg/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.

 
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