The molecular mechanisms responsible for the
hemostatic efficacy of recombinant
activated factor VII (
rFVIIa;
NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) in platelet-related
bleeding disorders remain unclear. The general concept is that
rFVIIa locally enhances
thrombin generation at the site of injury, where
tissue factor (TF) has become exposed. However, a growing amount of evidence shows that
rFVIIa is also able to exert its activity in a manner independent of TF. Using an in vitro flow model, we recently showed that TF-independent
thrombin generation is responsible for increased platelet deposition onto injured vessels following
rFVIIa administration. Furthermore, it has been shown that
rFVIIa can restore platelet aggregation in Glanzmann's
thrombasthenia (GT) patients via TF-independent
thrombin generation. However, the mechanism behind TF-independent
thrombin generation remains to be elucidated. It is postulated that, in vivo, both the TF-dependent and TF-independent
thrombin generation induced by
rFVIIa contribute to the control of
hemorrhage in patients with platelet-related
bleeding disorders and, perhaps, other causes of
hemorrhagic diatheses.