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Thromb Haemost 2004; 91(03): 531-537
DOI: 10.1160/TH03-07-0483
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Recombinant factor VIIa partially reverses the inhibitory effect of fondaparinux on thrombin generation after tissue factor activation in platelet rich plasma and whole blood

Grigoris T. Gerotziafas
1   Service d’Hématologie Biologique, Hôpital Hôtel-Dieu de Paris, France
2   LCL, Ivry sur Seine, France
,
François Depasse
2   LCL, Ivry sur Seine, France
,
Tahar Chakroun
1   Service d’Hématologie Biologique, Hôpital Hôtel-Dieu de Paris, France
,
Meyer M. Samama
1   Service d’Hématologie Biologique, Hôpital Hôtel-Dieu de Paris, France
2   LCL, Ivry sur Seine, France
,
Ismail Elalamy
1   Service d’Hématologie Biologique, Hôpital Hôtel-Dieu de Paris, France
› Author AffiliationsParts of this study have been presented as plenary lecture during the 17th International Congress on Thrombosis (Bologna, 26-30/10/2002) and as a poster presentation during the 44th American Society of Hematology Annual Meeting 2002.
Further Information

Publication History

Received 24 July 2003

Accepted after revision 05 February 2003

Publication Date:
05 December 2017 (online)

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Summary

Fondaparinux (Arixtra®), a specific AT-dependent FXa inhibitor, is effective and safe in the prevention and treatment of venous thromboembolism, but some major hemorrhagic events may occur. No specific antidote to fondaparinux has been proposed. Recombinant FVIIa (Novoseven®) could be used as an haemostatic treatment, but this option has not been well documented. We studied the effect of rFVIIa (1 µg/ml) on the inhibition of thrombin generation induced by fondaparinux (0.1µg/ml to 1 µg/ml). Coagulation was triggered in platelet rich plasma (PRP) or in whole blood by recalcification in the presence of diluted thromboplastin. In PRP thrombin generation was assessed using the thrombinoscope assay. In whole blood, prothrombin activation was assessed by measuring the kinetics of F1+2 formation using an ELISA assay. Fondaparinux at concentrations equal or greater than 0.5 µg/ml prolonged the initiation phase of thrombin generation, and reduced the velocity of prothrombin activation. It also decreased by 60% the endogenous thrombin potential. In the presence of fondaparinux (0.5 µg/ml to 1 µg/ml) rFVIIa accelerated the initiation phase of thrombin generation, but it did not significantly increase the endogenous thrombin potential. However, rFVIIa did not completely reverse the inhibitory effect of fondaparinux on the parameters of thrombin generation and prothrombin activation. This study shows that rFVIIa accelerates thrombin generation, but does not completely reverse the inhibitory effect of fondaparinux on thrombin generation. The potential clinical use of rFVIIa as haemostatic treatment of major bleedings related to fondaparinux has to be evaluated.

Keywords

Pentasaccharide - fondaparinux - thrombin generation - novoseven - tissue factor
 

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