Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors.

Recombinant factor (rF)VIIa has been available to clinicians since 1996 and has an excellent safety record after almost three-quarters of a million doses have been administered. This paper will review the current clinical experience with rFVIIa dosing in acquired and congenital hemophilia with inhibitors and chronicle all spontaneous and clinical trial reports of thrombotic adverse events as of April 2003. Standard dosing of rFVIIa (90 micro g kg(-1)) allows binding of FVIIa to the surface of an activated platelet and can directly activate factor X in the absence of tissue factor. Experience with bolus dosing suggests that higher dosing (>200 micro g kg(-1)) may be more efficacious in treating hemophilia patients. Clinical trials are ongoing to validate this observation. Continuous infusion dosing may be efficacious for major surgery but high infusion rates (50 micro g kg(-1) h(-1)) might be needed. The relationship between dose of rFVIIa, amount of thrombin generated and measurable FVIIa level is still not known and perhaps newer testing which measures thrombin generation might be more advantageous. Relatively few thrombotic events have been associated with rFVIIa. Known factors predisposing to thrombosis were present in 20 of the 25 (80%) hemophilia patients who were reported spontaneously or who developed a thrombosis during a clinical trial. Additionally, thrombotic events have not increased despite a growing experience with higher dosing of rFVIIa.