Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease

Abstract

Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this doubleblind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 g/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required. (Liver Transpl 2005;11:895-900.)

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

“…Previous observations are in line with the long lasting evidence that the PT is a poor predictor of peri-or post-operative bleeding in cirrhosis [15][16][17][18][19][20][21][22]. Furthermore, a powerful pro-hemostatic agent, such as recombinant activated factor VII (rFVIIa), although capable of considerably shortening the PT [23], proved to be ineffective to stop esophageal bleeding [23,24], or to reduce bleeding at surgery [25,26].…”

The role of recombinant factor VIIa in on-pump cardiac surgery: Proceedings of the Canadian Consensus Conference

“…17,20 In these studies rFVIIa was not associated with thromboembolic complications, but the number of such events was small, limiting the likelihood of finding such differences if they in fact were present.…”

Bleeding and Clotting Disorders in Pediatric Liver Disease

“…66 Clinical trials of rFVIIa in the treatment of active bleeding in liver transplantation have used doses ranging from 20-120 g/kg/dose on varying schedules. [67][68][69][70] The clinical efficacy of rFVIIa in the treatment of cirrhotic patients with variceal bleeding has been studied in 2 randomized, doubleblinded trials by Bosch et al, which showed no overall effect of rFVIIa versus placebo and no significant differences in reported mortality, incidence of adverse events, or treatment failure. 71,72 In the earlier trial, post hoc analysis of rFVIIa in patients with moderate to severe cirrhosis (Child-Pugh class B and C) and variceal bleeding showed a significant decrease in the number of patients in whom this failed to control the bleeding.…”

“…None showed any difference in mortality or thromboembolic adverse events (TAEs), and only one study showed a benefit of rFVIIa on decreasing RBC transfusion requirements. [66][67][68][69][70] Whereas rFVIIa has rarely been associated with TAEs when used for labeled indications, there has been concern with increased rates of TAEs with off-label use. A meta-analysis by Hsia et al of TAE rates across 22 clinical trials for various indications revealed a statistically significant increase in arterial thromboembolism, with a 4.5% rate in the rFVIIa-treated patients and a 2% rate with placebo.…”