Background: Aprotinin, a hemostatic agent,
regulates fibrinolysis, modulates the intrinsic coagulation pathway, stabilizes
platelet function, and exhibits anti-inflammatory properties through
inhibition of serine proteases, such as trypsin, plasmin, and kallikrein.
Aprotinin has been used successfully for many years in cardiac operations,
and there have been preliminary investigations of its use in hip
replacement operations. The objectives of this multicenter, randomized,
placebo-controlled, double-blind trial were to evaluate the efficacy
and safety of aprotinin as a blood-sparing agent in patients undergoing
an elective primary unilateral total hip replacement and to examine
its effect on the prevalence of deep-vein thrombosis in this population.
Methods: Seventy-three patients received a placebo;
seventy-six patients, a low dose of aprotinin (a load of 500,000
kallikrein inhibitor units [KIU]); seventy-five, a medium dose of
aprotinin (a load of 1,000,000 KIU, with infusion of 250,000 KIU
per hour); and seventy-seven patients, a high dose of aprotinin
(a load of 2,000,000 KIU, with infusion of 500,000 KIU per hour).
The end points for the determination of efficacy were transfusion
requirements and blood loss. Patients received standard prophylaxis
against deep-vein thrombosis and underwent compression ultrasonography
with color Doppler imaging of the proximal and distal venous systems
of both legs to evaluate for the presence of deep-vein thrombosis.
Results: Aprotinin reduced the percentages of
patients who required any form of blood transfusion (47 percent of
the patients managed with a placebo needed a transfusion compared
with 28 percent of those managed with low-dose aprotinin [p = 0.02],
27 percent of those managed with high-dose aprotinin [p = 0.008],
and 40 percent of those managed with medium-dose aprotinin [p =
0.5]). Only 6 percent (twelve) of the 212 patients treated with
aprotinin required allogeneic blood compared with 15 percent (ten)
of the sixty-eight patients treated with the placebo (p = 0.03).
Aprotinin decreased the estimated intraoperative blood loss (p =
0.02 for the low-dose group, p = 0.04 for the medium-dose group,
and p = 0.1 for the high-dose group), the measured postoperative
drainage volume (p = 0.4 for the low-dose group, p = 0.006 for the
medium-dose group, and p = 0.000 for the high-dose group), and the
mean reduction in the hemoglobin level on the second postoperative
day (thirty-four grams per liter for the placebo group, twenty-eight grams
per liter for the low-dose group [p = 0.000], twenty-six grams per
liter for the medium-dose group [p = 0.000], and twenty-three grams
per liter for the high-dose group [p = 0.000]). The rate of deep-vein
thrombosis was similar for all groups.
Conclusions: We concluded that aprotinin is
safe and effective for use as a hemostatic agent in primary unilateral total
hip replacements. In patients who are at high risk of receiving
allogeneic blood, use of aprotinin may be of particular clinical
and economic benefit.