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Submitted Oct 2, 2009; accepted Jul 18, 2010.
John R. Hoch, MD, Madison, Wisc
In 1999, the US Food and Drug Administration approved the
use of rVIIa for the treatment of bleeding in patients with hemo-
philia A or B and inhibitors of factors VII and IX. Since then, rVIIa
has been increasingly used off-label to treat surgical patients with-
out hemophilia that have intractable bleeding. Konc ˇar et al de-
scribe the largest case series of vascular patients treated with rVIIa.
Like numerous earlier case reports and case series, the current
article describes the use of rVIIa to decrease blood transfusion
requirements and correct coagulopathy after major operations
associated with serious nonsurgical bleeding.1,2The current series
also highlights a significant survival advantage for patients treated
with rVIIa compared to a historical control group. Similarly, a
meta-analysis of case series analyzing the use of rVIIa in major
abdominal operations found a 73% mean reduction or cessation of
bleeding and a 53% mean probability of survival after administra-
tion of rVIIa.1
Activated factor VII (VIIa) is believed to complex with tissue
factor in the subendothelium at sites of injury, leading to the
activation of factors IX and X and the generation of thrombin.3
Because of its mechanism of action, there exists the potential for
thrombotic complications which must be balanced with rVIIa’s
ability to control hemorrhage. Konc ˇar et al reported no thrombo-
embolic complications in their historical control or treatment
group. A review of the Food & Drug Administration’s Adverse
Event Reporting System between 1999 and 2004 for thromboem-
bolic adverse events (TAEs) with rVIIa, led the authors to con-
clude that there was a substantial risk of TAEs.4The majority of
TAEs occurred with the use of rVIIa for unlabeled indications, and
arterial thrombotic complications were the most common. A sub-
sequent meta-analysis of case series calculated a mean probability
of 16.5% for thrombemboli associated with rVIIa use during
abdominal surgery.1A recent meta-analysis of randomized con-
trolled trials comparing rVIIa to placebo found that TAEs oc-
curred in 8.6% of the rVIIa group compared to 6.4% in the placebo
group.2However, arterial TAEs occurred more frequently in the
rVIIa group compared to placebo. Despite the lack of TAEs in the
current article, a review of the literature would suggest that an
increased risk of thrombotic complications is suspected that can
only be ascertained by randomized controlled trials.
Konc ˇar et al’s routine use of rVIIa for intractable bleeding in
and elective thoracoabdominal aortic aneurysms (TAAAs) resulted
in a significant reduction in mortality rate (13%), a significant
decrease in transfusion requirement, and rapid correction of inter-
national normalized ratio compared to their retrospective histori-
cal control group. However, these results are not sufficient to
JOURNAL OF VASCULAR SURGERY
Volume 53, Number 4