title: Pediatric off-label use of recombinant factor VIIa.
abstract: OBJECTIVE
  Our goal was to report our institutional experience with recombinant factor VIIa for the treatment and/or prevention of bleeding in nonhemophiliac children.
  
  
  METHODS
  This was a retrospective case series in a tertiary pediatric referral hospital.
  
  
  RESULTS
  During 1999-2006, 135 patients received recombinant factor VIIa for off-label use. The median number of doses was 2; the median dose was 88 mug/kg. The most common diagnoses among patients receiving recombinant factor VIIa were disseminated intravascular coagulation/sepsis (28), surgical bleeding (19), procedural prophylaxis (16), and trauma (15). The median volume of blood products administered 24 hours before recombinant factor VIIa treatment was 29.7 vs 11.7 mL/kg 24 hours after treatment. Only 1 high-risk patient had significant bleeding after receiving prophylactic recombinant factor VIIa before an invasive procedure. Nonsurvivors had significantly increased incidence of multiple organ dysfunction syndrome (75%) compared with survivors (23%). The largest group of patients (n = 28) received recombinant factor VIIa for bleeding and/or coagulopathy because of disseminated intravascular coagulation; the mortality in this group was 26 (93%) of 28. Eleven patients received multiple doses of recombinant factor VIIa to treat bleeding complications after hematopoietic stem cell transplant, without improvement in blood use. Mortality in medical patients was 58% vs 16% in surgical patients. Three patients had significant thrombotic adverse events after receiving recombinant factor VIIa, resulting in 2 deaths and 1 leg amputation.
  
  
  CONCLUSIONS
  Off-label use of recombinant factor VIIa significantly decreases blood-product administration; surgical patients had control of life-threatening bleeding with low associated mortality. Prophylactic recombinant factor VIIa may be effective in preventing bleeding if given before invasive procedures in children at high risk. Prolonged use of recombinant factor VIIa for bleeding complications after hematopoietic stem cell transplant is not effective in preventing packed red blood cell transfusion. Presence of disseminated intravascular coagulation and mulitorgan dysfunction syndrome may help predict futility of recombinant factor VIIa treatment. Off-label use of recombinant factor VIIa is associated with thromboembolic events in children.
authors.affiliation: University of Alabama at Birmingham, 1600 7th Ave South, ACC 504, Birmingham, AL 35233, USA. jalten@peds.uab.edu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Alten
authors.forename: Kim
authors.initials: K
authors.lastname: Benner
authors.forename: Kelsey
authors.initials: K
authors.lastname: Green
authors.forename: Benjamin
authors.initials: B
authors.lastname: Toole
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Tofil
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Winkler
mesh_terms: D000293:Adolescent; D016063:Blood Loss, Surgical / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D015942:Factor VIIa / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D008297:Male; D010314:Partial Thromboplastin Time; D019106:Postoperative Hemorrhage / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D011292:Premedication; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications / Q000401:mortality
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa