Additive Effect of the Combined Administration of Low Molecular Weight Heparin and Recombinant Hirudin on Thrombus Growth in a Rabbit Jugular Vein Thrombosis Model

Bart J Biemond; Marcel Levi; Michael T Nurmohanned; Harry R Büller; Jan W ten Cate

doi:10.1055/s-0038-1648874

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1994; 72(03): 377-380
DOI: 10.1055/s-0038-1648874

Original Article

Schattauer GmbH Stuttgart

Additive Effect of the Combined Administration of Low Molecular Weight Heparin and Recombinant Hirudin on Thrombus Growth in a Rabbit Jugular Vein Thrombosis Model

Authors

Bart J Biemond

The Center for Flemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
Marcel Levi

The Center for Flemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
Michael T Nurmohanned

The Center for Flemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
Harry R Büller

The Center for Flemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
Jan W ten Cate

The Center for Flemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands

Abstract

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Summary

Recombinant Hirudin (r-Hirudin) is a new anticoagulant with specific antithrombin activity independently of antithrombin III. Low molecular weight heparins (LMWH) exert predominantly anti-Xa activity. Therefore, we hypothesized that combined administration of r-Hirudin and LMWH would induce a stronger antithrombotic effect as compared to r-Hirudin administered alone or combined with unfractionated heparin. To assess the effect on thrombus growth, we determined the accretion of ^l25I-labeled fibrinogen onto autologous non-radioactive thrombi preformed in the jugular veins of rabbits. The rabbits received unfractionated heparin (80 anti-factor Xa U), LMWH (80 anti-factor Xa U) or r-Hirudin (0.3, 5.0 and 10.0 mg/kg) either separately or by combined infusion for a 3 h period.

R-Hirudin reduced the thrombus growth in a dose dependent fashion. The combined administration of 80 anti-Xa U LMWH and r-Hirudin at a dose of 0.3 mg/kg resulted in a stronger antithrombotic effect as compared to the combined infusion of unfractionated heparin and r-Hirudin (thrombus growth: 14.3% ± 6.0 vs 28.9% ± 6.5; p = 0.001). This difference in additive antithrombotic effect of 80 anti-Xa ULMWH versus unfractionated heparin on r-Hirudin was also observed when LMWH was combined with 5.0 mg/kg and 10.0 mg/kg r-Hirudin versus unfractionated heparin combined with r-Hirudin (thrombus growth: 16.4% ± 1.6 vs 29.1% ± 3.9; p = 0.01 and 10.1% ± 1.8 vs 20.4% ± 4.5; p = 0.001, respectively).

In conclusion, this study showed an additive antithrombotic effect of LMWH on the thrombus growth reducing effect of r-Hirudin. This may potentially be of clinical interest, i. e. much lower doses of r-Hirudin may be used to achieve a similar effective anticoagulant effect when combined with LMWH.

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