rFVIIa is approved for treatment and prevention of bleeding in patients with hemophilia A or B with inhibitors to factor VIII or factor IX, in patients with acquired hemophilia, and in patients with congenital factor VII deficiency.
Although rFVIIa is increasingly used to manage uncontrolled hemorrhage in clinical settings outside these licensed indications, there are no randomized controlled trials of its safety and efficacy in pediatric patients.
Dr. Zoe K. McQuilten from Monash University, Melbourne, Victoria, Australia and colleagues reviewed the off-label use of rFVIIa in all pediatric patients entered into the Haemostasis Registry. Their findings appear in the May 28th online issue of Pediatrics. [
From 2003 to 2009, 388 patients under age 16 years (median, 12 months; range, 9 hours to 16 years) received rFVIIa, mostly for active bleeding (377 patients, 97%), but occasionally as prophylaxis for surgery (11 patients, 3%).
Compared to the period before administration of rFVIIa, there was a reduction in the volume of red blood cells, platelets, fresh frozen plasma, and cryoprecipitate transfused in the 24 hours after administration of rFVIIa. More than four in five patients (275 of 335 patients with data, 82%) responded to treatment with rFVIIa.
Response rates were higher when rFVIIa was used to manage bleeding in the context of a surgical procedure (92%) than when used for nonsurgical indications (61%), and in multivariable analysis, lower pH or use in a nonsurgical clinical context was associated with a lower likelihood of response.
Mortality at 28 days was significantly higher among nonresponders (67%) than among responders (14%) and among patients who received rFVIIa in a surgical context (21%) than among patients who received rFVIIa in a nonsurgical context (44%).
Twenty-one patients (5.4%) experienced a thromboembolic adverse event (TEA), but there was no apparent relationship between the dose or number of doses of rFVIIa and the risk of TEA.
Results were similar, if not better, in the largest subgroup of patients, those who received rFVIIa in the setting of cardiac surgery (202 patients, 52%).
“Despite the observed reduction in transfusion requirements,” the researchers note, “it is difficult to make conclusions regarding the efficacy of rFVIIa from our data. Other interventions used at the same time as rFVIIa administration may account for the reduction in blood product usage and subjective bleeding assessment, and no control group is available for comparison.”
“Although randomized controlled studies are needed to evaluate the efficacy and safety of rFVIIa use in off-label indications, there are both practical and ethical challenges in conducting such studies in pediatric patients with uncontrolled hemorrhage,” the investigators conclude. “In the absence of such studies, registry data reporting current practice across a large number of hospitals is valuable for identifying trends in outcomes and adverse events.”