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 micro g/ml) on the inhibition of
thrombin generation induced by
fondaparinux (0.1 micro g/ml to 1 micro g/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 F(1+2) formation using an ELISA assay.
Fondaparinux at concentrations equal or greater than 0.5 micro g/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 micro g/ml to 1 micro g/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.