Off-label recombinant factor VIIa use and thrombosis in children: a multi-center cohort study

J Pediatr. 2011 May;158(5):820-825.e1. doi: 10.1016/j.jpeds.2010.10.038. Epub 2010 Dec 10.

Abstract

Objective: To describe the off-label use of recombinant factor VIIa (rFVIIa) in tertiary care pediatric hospitals across the United States and to assess thrombotic events.

Study design: A retrospective multi-center cohort study using the Pediatric Health Information System administrative database. Children 18 years of age or younger who received rFVIIa between 2000 and 2007 were included. A label admission was defined as an admission with an International Classification of Diseases diagnostic code for hemophilia or factor VII deficiency; admissions without these codes were classified as off-label.

Results: There were 4942 rFVIIa admissions, representing 3764 individual subjects; 74% (3655) of the admissions were off-label. There was a 10-fold increase in the annual rate of off-label admissions from 2000 to 2007 (from 2 to 20.8 per 10 000 hospital admissions, P < .001). The mortality rate in the off-label group was 34% (1258/3655). Thrombotic events occurred in 10.9% (399/3655) of the off-label admissions.

Conclusions: The off-label use of rFVIIa in hospitalized children is increasing rapidly despite the absence of adequate clinical trials demonstrating safety and efficacy. Thrombotic events are common and mortality is high among patients receiving off-label rFVIIa. Further studies are warranted to determine whether these adverse events are attributable to rFVIIa.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Factor VIIa / adverse effects*
  • Factor VIIa / therapeutic use
  • Female
  • Follow-Up Studies
  • Hemophilia A / drug therapy*
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Male
  • Off-Label Use*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Survival Rate / trends
  • Thrombosis / chemically induced
  • Thrombosis / epidemiology*
  • United States / epidemiology

Substances

  • Recombinant Proteins
  • recombinant FVIIa
  • Factor VIIa