The Use of Recombinant Factor VIIa*

As described in detail in other chapters of this volume, conditions with excessive bleeding, as are seen with uterine rupture, placenta accreta, abruption and uterine atony, often require intensive resuscitation with blood components and coagulation factors. In such circumstances, blood transfusion may be life-saving, but on occasion involves exposing the patient to additional risks. Over the years, numerous efforts have been put forward to reduce these risks. One of the most spectacular is discussed in this chapter. Recombinant activated factor VII (rFVIIa) (NovoSeven®; Novo Nordisk A/S, Bagsvaerd, Denmark) was developed for the treatment of spontaneous and/or surgical bleeding episodes in patients with hemophilia A or B with formation of allo-antibodies to FVIII or FIX after replacement therapy1–3. rFVIIa is currently licensed for this indication in most countries world-wide. The US Food and Drug Administration (FDA) licensed rFVIIa on March 25, 1999 for bleeding episodes in patients with hemophilia A or B and inhibitors to FVIII or FIX. The FDA approved use of rFVIIa in 2005 for additional indications such as surgical procedures in patients with hemophilia A or B and inhibitors, and treatment of bleeding episodes in patients with factor VII deficiency4. In Europe, it is also approved for use in bleeding episodes in patients with acquired hemophilia due to auto-antibodies against endogenous FVIII or FIX, surgical procedures in this group of patients, and Glanzmann’s thrombasthenia. Beyond its currently recognized indications, rFVIIa has been effectively used ‘off label’ on an empirical basis as a general hemostatic agent in a wide range of conditions associated with acute, uncontrolled, or otherwise profound bleeding, and in other clinical circumstances associated with excessive bleeding in patients without pre-existent coagulation defects5,6. Indeed, the early descriptions of the benefits of rFVIIa in trauma patients7–9 were bolstered by a compassionate use study, which suggested that rFVIIa administration could reverse massive bleeding, and thus significantly decrease transfusion requirements observed in critically ill, multi-transfused trauma patients10,11. Recently, rFVIIa was approved for the treatment of hemorrhage associated with congenital factor VII deficiency12,13 and Glanzmann’s thrombasthenia14,15.