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  • Title: Tissue factor-independent effects of recombinant factor VIIa on hemostasis.
    Author: Weeterings C, Lisman T, de Groot PG.
    Journal: Semin Hematol; 2008 Apr; 45(2 Suppl 1):S12-5. PubMed ID: 18544417.
    Abstract:
    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.
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