This supplement contains proceedings from the Sixth Novo Nordisk Symposium on the Treatment of Bleeding and Thrombotic Disorders held on May 3 and 4, 2001 in Copenhagen, Denmark. The objectives of the meeting, as addressed in this supplement, were to discuss the current state-of-the-art and latest advances surrounding the use of recombinant activated factor VII (rFVIIa, NovoSeven®) in hemostasis management, to identify the central role of platelets in promoting hemostasis, to discuss the clinical use of rFVIIa in conditions of impaired coagulation, and to assess the efficacy and safety of rFVIIa as a hemostatic agent.
The application of rFVIIa in hemostasis management and in various clinical scenarios is a direct result of the increased knowledge of the process of coagulation and, in paticular, its initiation by the tissue factor (TF)/FVIIa pathway. In the opening session, Dr Østerud examines the role of platelets in hemostasis. New aspects in the understanding of coagulation are presented by Drs Hoffman and Monroe, who have used an in vitro model to demonstrate the mechanism of action of rFVIIa. These data support the view that addition of high levels of exogenous FVIIa enhance the rate of thrombin generation. Galán et al and Kjalke et al present data showing the pivotal role played by platelets during clot formation.
rFVIIa is now recognized as the state-of-the-art drug for the treatment of hemophilia patients with inhibitors and an overview of the use of rFVIIa in these patients is presented by Dr Shapiro. The clinical use of rFVIIa in other coagulation disorders has previously been reported. Poon et al add to this information in their presentation on the use of rFVIIa in patients with Glanzmann's thrombasthenia. The in vitro data of Galán et al and Kjalke et al support the effects of rFVIIa in thrombocytopenia-like and thrombocytopathic conditions.
The clinical flexibility of rFVIIa is not limited to hemostasis management. Active site-inhibited seven (ASIS) is a modified version of rFVIIa in which the catalytic site has been irreversibly blocked by the synthetic tripeptide (Phe-Phe-Arg) chloromethyl ketone. ASIS is a competitive inhibitor of TF and its ability to block coagulation gives it antithrombotic potential. Dr Petersen describes the mode of action of ASIS including signal transduction. The presentation by Welty-Wolf et al describes the value of tissue factor blocking by ASIS in animal models of acute lung injury.
The future potential of rFVIIa as a product for hemostasis management is proving to be an exciting and rewarding field of study. In the next 2 years, new indications appropriate to the use of rFVIIa are likely to emerge and undergo scrutiny. Ongoing studies to explore the underlying mechanism of rFVIIa and the optimal dosage regimen are likely to increase the clinical effectiveness and safety of this extraordinary drug.
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