Grand Rounds: Using activated factor VII in ob/gyn practice

Key Points

Activated recombinant FVII (rFVIIa) was originally approved by the FDA to treat bleeding episodes in hemophilia patients with inhibitors, and patients with congenital deficiency of factor VII. But for ob/gyns, the real interest lies in the drug's apparent ability to manage uncontrolled hemorrhaging. Before we delve into the research supporting these off-label uses, however, we'll take a closer look at the role of rFVIIa in the clotting cascade.

How does this clotting factor work?

rFVIIa acts in two stages and on two surfaces; both activities occur mainly at the site of injury. Although the agent has little or no systemic activity-even with the administration of large supraphysiologic doses-its local effects indirectly have profound systemic effects, exerting an influence on Tissue Factor (TF)-bearing cell surfaces and thrombin-activated platelets.

When is rFVIIa indicated?

As mentioned before, rFVIIa was originally intended for the treatment of hemophilia patients who have developed inhibitors.¹ The risk of joint bleeding and trauma in these patients puts them at an increased risk of hemorrhage. Unfortunately, they don't respond to factor replacement therapy, which is why rFVIIa was developed, namely to prevent chronic joint disabilities from repeated bleeding in joints, and to cover surgical procedures.

Patients with other severe bleeding conditions have benefited from rFVIIa, as well. Glanzmann's thrombasthenia is a rare inherited hematologic disorder defined by deficiency or abnormality of the glycoprotein IIb-IIIa complex. It is seen among four distinct communities: French Gypsies, Iraqi Jews settled in Israel, Indians, and Arabs of Jordanian origin. Spontaneous bleeding is rare in this disorder but bleeding due to minor trauma or heavy bleeding during menstruation and pregnancy can occur. Although rFVIIa is not 100% effective,² physicians should be aware of it as an alternative treatment because many of these patients don't respond to platelet transfusions due to the development of alloantibodies. There are numerous anecdotal reports of the successful use of rFVIIa in Glanzmann's patients during menorrhagia and pregnancy.^3,4

Similarly rFVII has been used to control bleeding in cardiac surgery, orthopedic surgery, in surgical patients with massive bleeding, and in trauma patients.⁵ While giving rFVIIa to trauma patients has also been found to significantly reduce the need for transfusion, this advantage was not statistically significant among those with penetrating wounds.⁶ Currently, a phase III trial for use of rFVIIa in trauma is underway in the United States.

Activated recombinant factor VII has been used in cardiac surgery in both children and adults, where it significantly reduced the need for blood transfusion. There have been two small prospective, randomized clinical trials using rFVIIa in orthopedic surgery. The requirement for blood and blood components were 46% in the rFVIIa group, compared with 67% in the placebo group (P=0.24). rFVIIa was not associated with any adverse side effects. Other surgical situations where rFVIIa has been documented in trials include prostatectomy, hepatic resection, and surgical correction of burns. In a pilot study done to investigate the effect of rFVIIa in burn patients undergoing excision and skin grafting, patients on rFVIIa seemed to need fewer blood transfusions (P=0.004).