Thromb Haemost 2006; 96(04): 446-453
DOI: 10.1160/TH06-04-0205
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

A direct thrombin inhibitor studied by dynamic whole blood clot formation

Haemostatic response to ex-vivo addition of recombinant factor VIIa or activated prothrombin complex concentrate
Benny Sørensen
1   Center for Haemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark
,
Jørgen Ingerslev
1   Center for Haemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark
› Institutsangaben

Financial support: This study was supported by a grant (#22–03–0386) from the Danish Research Agency as well as by an unrestricted grant from Astra Zeneca.
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Publikationsverlauf

Received 12. April 2006

Accepted after resubmission 05. August 2006

Publikationsdatum:
29. November 2017 (online)

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Summary

Direct thrombin inhibitors have proven efficacious in prevention of venous thromboembolism. Bleeding complications are rare, but in case of acute serious bleeding, an effective and instant haemostatic intervention may be required. In the present study it was demonstrated that the direct thrombin inhibitor melagatran induces dose-dependent abnormalities in whole blood (WB) clotting profiles as recorded bya recently described modified thrombelastographic model, and that rFVIIa or APCC are capable of improving the haemostatic capacity. Experiments were performed using WB from 30 healthy males. In-vitro titration experiments (n=10) with addition of melagatran to WB corresponding to plasma concentrations ranging from 0 to 5.0 µM (12 steps) showed a dose-dependent prolongation of the clot initiation and characteristic decrease of the maximum rate of clot propagation. In-vitro intervention studies (n=20) were completed with four different concentrations of melagatran as well as addition of four different levels of rFVIIa or APCC. At all tested concentrations of melagatran, rFVIIa significantly shortened the melagatran-induced prolonged clot initiation but induced only minor improvements of the reduced clot propagation. In contrast, APCC significantly and dose-dependently shortened the clot initiation and accelerated the clot propagation. In conclusion, our thrombelastographic model appears useful for evaluating the effect of direct thrombin inhibitors on dynamic WB clot formation and rFVIIa, but especially APCC significantly improved theWB clot formation. The pronounced stabilizing effect of APCC may be caused by its content of prothrombin and activated coagulation factors.