Objective: Recombinant activated factor VII (rFVIIa) in controlling the pre-existing life-threatening bleeding and in preventing excessive bleeding among pediatric patients undergoing invasive surgeries, was evaluated.
Methods: An open-label, prospective uncontrolled study of rFVIIa (Novo Nordisk A/S Bagvaerd, Denmark) was conducted between January 2000 to July 2004. A bolus injection of 40–100 μg/kg of rFVIIa as a single or repeated doses at 15–30 min was given until the bleeding significantly reduced, followed by 40 μg/kg at 4 h interval until the bleeding was completely ceased. The patients were divided into 2 groups. Group 1 consisted of 11 patients receiving rFVIIa for controlling pre-existing life-threatening bleeding unresponsive to conventional replacement therapy at pre-(n=1), intra-(n=1) and post-operation (n=9). The median blood loss was 2.2 ml/kg/min at the median duration of 3 h prior to rFVIIa administration. Group 2 consisted of 9 patients receiving rFVIIa for preventing excessive bleeding from invasive surgeries. The surgeries included exploratory laparotomy (n=5), surgery of cardiac (n=5), liver (n=4), brain (n=2) and lung (n=1), liver transplantation (n=1), orthopedic corrective surgery of scoliosis (n=1), and orbital translocation (n=1).
Result: Two patients were the premature neonate of 1,120 and 675 g in the first 24 h of life and 17 were children with a median age of 5 years. One patient had two subsequent surgeries, 6 months apart. They had no pre-existing hemostatic disorders. Patients in group 1 were in the state of threatened shock to profound shock. Due to massive transfusion, they exhibited dilutional coagulopathy and thrombo-cytopenia. The treatment was considered effective response in 17 cases (17/20=85%), including 8 patients (8/11=72.7%) in group 1 and 9 patients (9/9=100%) in group 2. They had a complete cessation of bleeding with no recurrence. Ineffective responses were found in 3 patients (3/20=15%) in group 1. One patient exhibited massive pulmonary hemorrhage from complicated lobar pneumonia which was unresponsive to right lower lung lobectomy. The other two patients, whose bleeding temporarily slowed down, required the re-explorations revealing a tear at the right atrium and a leak at the hepatic anastomosis site respectively. Although the rFVIIa combined with adequate amounts of blood components were given, the median intra-operative blood loss among 4 patients in group 1 was 0.3 ml/kg/min which was significantly higher than that of group 2 (0.1 ml/kg/min) p=0.014. The median total dose of rFVIIa in group 2 (60 μg/kg) was significantly lower than that in group 1 (120 μg/kg) p=0.037. Ultimately, 2 patients died while all patients in group 2 survived. No clinical evidences of thrombo-embolic complication were observed.
Conclusion: The rFVIIa seems to be effective in controlling life-threatening bleeding and in preventing excessive bleeding in a limited series of pediatric patients undergoing invasive surgeries. Further study is warranted.