The further development of rFVIIa during the 2000s showed no safety problems by using a dose of 270 µg/kg rFVIIa administered as a bolus instead of the 90 µg/kg in three doses with a 2- to 3-hour interval previously recommended. Based on the clinical experiences late in the 1990s, it was obvious that some patients required higher doses to stop an upcoming bleeding with one single injection. Furthermore, an increased clearance rate of rFVIIa was found in children. Thus, the higher dose was recommended in children and in patients with heavy bleedings. Furthermore, the large distribution volume of rFVIIa observed already early in the 1990s was followed-up by studies of the extravascular distribution of rFVIIa in mice. Intravenously injected rFVIIa disappeared quickly from the blood and could be traced to various tissues, in some up to 7 days after injection. This would indicate a mechanism for a long-term hemostatic effect in stopping microhemorrhages in the microvasculature. A trial with daily doses of rFVIIa also showed a decrease of joint bleeds in a group of heavily bleeding hemophilia patients with inhibitors.