Abstract
Background: Although recombinant factor VIIa is often utilized to mitigate critical bleeding following cardiac surgery, the optimal dosing strategy in this population is not well-established. At our institution, hospital guidelines recommend administration of recombinant factor VIIa 60 mcg/kg for all off-label indications. However, available data suggest doses as low as 17 mcg/kg have been efficacious in cardiac surgery patients with critical bleeding. Additionally, although low-dose recombinant factor VIIa (< 40 mcg/kg) and high-dose (50-109 mcg/kg) dosing strategies have been reported equally efficacious according to retrospective, observational studies, higher doses may be associated with increased incidence of adverse events. Therefore, we aimed to evaluate the safety of recombinant factor VIIa in cardiac surgery patients with critical bleeding, and estimate potential cost-savings associated with implementation of a low-dose recombinant factor VIIa protocol in this population.
Methods: All adult cardiac surgery patients who received one or more doses of recombinant factor VIIa during a 1-year period (July 1, 2016 to June 30, 2017) were included. Thromboembolic event rates documented within 14 days following recombinant factor VIIa administration were evaluated in patients alive at discharge. An average wholesale price of 2.59 USD per mcg was utilized for recombinant factor VIIa cost calculations.
Results: A total of 16 patients received 24 doses of recombinant factor VIIa during the study period. The median weight-based dose administered was 55 mcg/kg (utilizing actual body weight), and the median dose was 5 mg. The median cost per recombinant factor VIIa dose was 12,950 USD, resulting in a total expenditure of 277,174 USD. Nine of sixteen patients (56%) survived to hospital discharge. Five of nine (56%) patients alive at discharge experienced thromboembolic complications following recombinant factor VIIa administration, three (60%) of which were central nervous system (CNS) thromboembolic events. Based on data supporting low-dose strategies, a proposed weight-based recombinant factor VIIa dose-minimization protocol was developed by leadership in the departments of pharmacy, hematology, cardiac surgery, and cardiac anesthesia (Table 1). Implementation of this protocol would result in an estimated annual cost-avoidance of 168,376 USD.
Conclusions: Recombinant factor VIIa administration at a dose of 55 mcg/kg in adult cardiac surgery patients with critical bleeding is associated with a high rate of thromboembolic events, including CNS thromboembolism. Additionally, this recombinant factor VIIa dosing strategy is associated with significant cost, which can be substantially reduced with implementation of a low-dose recombinant factor VIIa protocol in the cardiac surgery population.
No relevant conflicts of interest to declare.
