A multicenter assessment of recombinant factor VIIa off-label usage: Clinical experiences and associated outcomes

Abstract

BACKGROUND: Off-label use of recombinant factor VIIa (rFVIIa) occurs despite minimal data. The purpose of this study was to describe prescribing practices and clinical outcomes for off-label rFVIIa use. STUDY DESIGN AND METHODS: A retrospective, multicenter chart audit of 315 nonhemophiliac patients was performed. RESULTS: Off-label indications included prevention of bleeding primarily related to procedural manipulation in 37.8 percent of patients and treatment of bleeding in 62.2 percent of patients. Baseline coagulopathy was present in 79.7 percent of patients. Prescriber specialty varied. The median doses for prevention and treatment were 75.6 and 89.4 μg per kg, respectively (p = 0.0006). The international normalized ratio (INR) decreased (p < 0.0001) from baseline in both groups. Transfusions of blood products were provided to 85.1 percent of patients before rFVIIa administration with considerable practice variation. Few patients received other procoagulant agents. In the prevention group, 14.3 percent of patients bled within 6 hours of their procedure. No variable was independently associated with bleeding prevention. In the treatment group, 52.6 percent of patients stopped bleeding within 6 hours of rFVIIa administration. The only independent variable associated with bleeding cessation was an arterial pH value of less than 7.20, which was a negative predictor (odds ratio, 0.207; 95% confidence interval, 0.084-0.507). Possible rFVIIa-associated adverse events occurred in 9.8 percent of patients and primarily involved undesirable clotting. No variable was independently associated with adverse events. CONCLUSIONS: Off-label use of rFVIIa includes prevention and treatment of bleeding. rFVIIa is associated with INR reduction. Bleeding is rare with prophylactic rFVIIa but the cessation of bleeding is less than reported in the literature and may be related to pH. Possible adverse events are related to undesirable clotting.