Abstract
Recombinant activated factor VIIa (rFVIIa) is a prohemostatic agent initially approved
for use in hemophilia patients with inhibitors and recently for Glanzmann thrombasthenia.
Despite its approval indications, rFVIIa has also been used for a diverse range of
off-label indications to treat bleeding related to traumatic injury, major hemorrhage
following surgery, intracranial hemorrhage, and for uncontrolled bleeding as a prothrombotic
hemostatic agent. Despite its off-label use, the benefit of rFVIIa in most nonhemophilia
settings remains uncertain as the majority of clinical trials have not consistently
demonstrated beneficial effects as determined by reduced bleeding, decreased blood
product utilization, or have not demonstrated a mortality benefit. As with any prohemostatic
agent, the risk of thromboembolic events is increased when rFVIIa is used off-label.
Pooled data from randomized nonhemophilia studies report an increased risk in the
elderly for arterial thromboses, although most individual trials have been underpowered
to determine adverse thrombotic events. The causes of thrombotic adverse events associated
with off-label use of rFVIIa may be due to an increased risk of adverse events due
to critical illness or due to higher doses of rFVIIa used in off-label trials. Without
clearly supportive data, physicians should consider risk versus benefit and exercise
restraint using rFVIIa in off-label settings. Further, evidence-based guidelines should
be developed by professional organizations, and additional randomized controlled clinical
trials are needed to further assess the efficacy and safety of off-label rFVIIa use.
Keywords
recombinant activated factor VIIa - hemorrhage - coagulopathy - prothrombotic - surgery
- thrombosis
