Off-label use of recombinant factor VIIa in pediatric patients.
ABSTRACT To examine off-label recombinant factor VIIa (rFVIIa) use in pediatric patients including clinical indications, dose, adverse events, and outcomes.
All pediatric patients entered into the Haemostasis Registry from 75 participating hospitals were analyzed.
Three hundred and eighty-eight pediatric patients received off-label rFVIIa from 2003 to 2009. Median age was 12 months (interquartile range 1 month to 11 years). Clinical context included cardiac surgery (52.1%), medical (11.6%), other surgery (10.8%), hematology/oncology (10.3%), trauma (9.3%), intracranial hemorrhage (3.1%), and liver disease (2.8%). Twenty-six patients received extracorporeal membrane oxygenation at the time of rFVIIa administration. Median first dose was 114 μg/kg (interquartile range 90-181; range 7-2250). Thirty-four percent received >1 dose. There was a reduction in usage of red blood cells, platelets, fresh-frozen plasma, and cryoprecipitate in the 24 hours after the first dose for all patients (all P values < .001). Thromboembolic adverse events (TEAs) were reported in 5.4%. No association between TEA and size of first dose was found. Where data were available, 82% of patients were subjectively classified as responding to rFVIIa. Overall 28-day mortality was 27%. In multivariate analysis, pH values before administration and clinical context were independently associated with response to first dose and 28-day mortality.
There was a significant reduction in blood product administration after rFVIIa and a subjective response rate of 82%. Both pH and clinical context were associated with response to rFVIIa and mortality. Overall, 5.4% had a TEA reported.
Article: Use of Recombinant Activated Factor VII for Controlling Refractory Postoperative Bleeding in Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass[show abstract] [hide abstract]
ABSTRACT: Objective: To review the efficacy, safety, and dose of recombinant activated factor VII in off-label management of refractory bleeding in pediatric patients with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. Design: A retrospective database analysis with medical records review. Setting: A single research hospital. Participants: Ninety pediatric patients with uncontrolled postoperative hemorrhage after cardiac surgery with cardiopulmonary bypass for congenital heart disease. Interventions: Intravenous recombinant activated factor VII treatment according to institutional treatment protocol. Measurements and Main Results: The recombinant activated factor VII treatment was effective in reducing bleeding in 78 pediatric patients. The 12 patients who failed to respond had surgical sources of bleeding. The mean blood loss decreased from 51.04 mL/kg/2 h to 7.8 mL/kg/2 h (p < 0.001) in neonates, from 40.2 mL/kg/2 h to 7.7 mL/kg/2 h (p < 0.001) in infants, and from 29.1 mL/kg/2 h to 4.0 mL/kg/2 h in children (p < 0.001). The mean (standard deviation) total recombinant activated factor VII doses required to achieve hemostasis were 131.7 (69.8) �g/kg in neonates, 104.6 (36.0) �g/kg in infants, and 44.6 (15.3) �g/kg in children aged 1 to <18 years. There was no evidence of thrombosis in the first 24 hours after the administration of recombinant activated factor VII. Conclusions: Recombinant activated factor VII treatment reduced blood loss and transfusion requirements and prevented re-exploration in the majority (83.8%) of pediatric cardiac surgery patients. High doses were required to discontinue bleeding promptly in neonates, the majority of whom had hypoplastic left-heart syndrome. No treatmentrelated thrombotic events were observed.Journal of Cardiothoracic and Vascular Anesthesia 12/2011; 25(6):987-94.. · 1.64 Impact Factor