Recombinant factor VIIa as an antidote for anticoagulant treatment

Increasing knowledge on the function of the hemostatic system in vivo and limitations of currently available anticoagulant agents have led to the development of a new generation of anticoagulants. These new agents have a greater specificity towards activated coagulation pathways and factors and are presently being evaluated in clinical studies. The new generation anticoagulants include specific inhibitors of factor IIa (melagatran), factor Xa (pentasaccharides), and agents that interfere with tissue factor (TF) activity. A limitation of this new class of anticoagulants may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs. Recombinant factor VIIa (rFVIIa) is a potent prohemostatic agent and may represent an interesting option for consideration when an antidote is required. Indeed, rFVIIa has proven to be efficacious in the reversal of anticoagulant treatment with vitamin K antagonists. Studies in healthy subjects have also revealed that rFVIIa administration corrects coagulation time and can induce thrombin generation during anticoagulation with pentasaccharides or TF-inhibiting therapy. These results indicate that rFVIIa infusion results in a prohemostatic response in vivo in patients receiving treatment with factor Xa- or TF-specific anticoagulants. This suggests that rFVIIa may be a good candidate as an antidote for new anticoagulants in cases of (severe) bleeding or in patients scheduled for emergency surgery.