Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

Abstract

on behalf of the International Study Group on rFVIIa in UGI Hemorrhage A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B ‫؍‬ 26%, C ‫؍‬ 74%) were randomized equally to: placebo; 600 g/kg rFVIIa (200 ؉ 4؋ 100 g/kg); or 300 g/kg rFVIIa (200 ؉ 100 g/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P ‫؍‬ 0.37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 g/kg rFVIIa compared with placebo (odds ratio 0.31, 95% confidence interval ‫؍‬ 0.13-0.74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 g/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups. Conclusion: Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups. (HEPATOLOGY 2008;47:1604-1614

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].…”

“…rFVIIa promotes hemostasis by binding to the surface of platelets activated at sites of vascular injury, and by directly activating factor X [24,119,120]. In patients with and without liver diseases, administration of rFVIIa shortened the abnormal PT value [119][120][121][122][123][124].…”

“…In patients with and without liver diseases, administration of rFVIIa shortened the abnormal PT value [119][120][121][122][123][124]. However, in randomized clinical trials rFVIIa administration to patients with cirrhosis proved ineffective in controlling bleeding from varices or bleeding during surgery [24,120,[125][126][127].…”

Coagulation in chronic liver disease and the use of prothrombin complex concentrate for an emergent procedure: a case report and review of literature

“…One study found that when analyzed at different laboratories, the use of different PT reagents and laboratory equipment at different laboratories was found to account for a 26% difference in INR values from the same individuals with cirrhosis [13]. Given a tenuous balance of a disrupted procoagulatant and anticoagulant factor synthesis in liver disease, increasing INR values may reflect worsening synthetic function of the liver, but does not necessarily reflect a higher propensity for bleeding events and only reflects the procoagulant side of this balanced equation [14]. Lowering or normalizing INR values in patients with bleeding events, such as variceal bleeding, does not lead to improved outcomes or decreased failure rates in hemorrhage control [15].…”

Letter: proton pump inhibitors ‐ severity of liver disease and mortality in patients with cirrhosis

“…Actually, the 6-week mortality rate due to variceal bleeding is 15-20%, and in patients with severe decompensated cirrhosis, the mortality rate increases up to 30%. [6][7][8] The authors did not describe the bleeding or re-bleeding rate during follow-up, although variceal bleeding was one of the main reasons of death in that study. As mentioned in the paper, PPI was given to patients without strong indications (epigastric pain, nausea or vomiting).…”