Tissue factor-independent effects of recombinant factor VIIa on hemostasis

Cees Weeterings, Ton Lisman, Philip G. de Groot*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

The molecular mechanisms responsible for the hemostatic efficacy of recombinant activated factor VII (rFVIIa; NovoSeven (R), 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.

Original languageEnglish
Pages (from-to)S12-S15
Number of pages4
JournalSeminars in hematology
Volume45
Issue number2
DOIs
Publication statusPublished - Apr-2008
Event9th Novo Nordisk Symposium on Haemostasis Management - , Spain
Duration: 15-Nov-200716-Nov-2007

Keywords

  • DOSE FACTOR-VIIA
  • GLYCOPROTEIN IB
  • FACTOR-X
  • GLANZMANNS-THROMBASTHENIA
  • PLATELET-AGGREGATION
  • THROMBIN GENERATION
  • ACTIVATION
  • HEMOPHILIA
  • MECHANISM
  • COMPLEX

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