title: Risk of bleeding and inhibitor development after circumcision of previously untreated or minimally treated severe hemophilia A children.
abstract: BACKGROUND
  Surgery and intensive factor VIII (FVIII) replacement may be risk factors for development of inhibitors.
  
  
  OBJECTIVE
  To evaluate time and rate of inhibitor development postcircumcision over 12-month period, and to assess bleeding of children with severe hemophilia A after low-dose FVIII replacement and local hemostasis.
  
  
  METHODS
  Sixty-one previously untreated patients (PUPs) or minimally treated patients (MTPs) with severe hemophilia A less than 36 months were enrolled; 25 underwent circumcision during the 18-month enrollment period, and 36 matched patients were not circumcised. All patients were treated on demand with plasma-derived FVIII, and all were inhibitor negative at the time of enrollment. Intron 22 inversion was analyzed. A potent hemostatic agent (gelatin sponge) was applied on the site of surgery, and then dressed with gauze. Two doses of FVIII concentrate (25 U/kg) were given, 1 hour before circumcision and 1 hour before removal of dressing. The inhibitor was determined every 8 exposure days (EDs).
  
  
  RESULTS
  None of the patients had bleeding or infection, except one who had minimal transient bleeding 8 days after surgery, and was treated easily by a single dose of FVIII (50 U/kg). After a median of 16 EDs, high-titer inhibitors developed in seven patients: three patients in the circumcised group (12%) in contrast to four patients (11.1%) in the noncircumcised group.
  
  
  CONCLUSIONS
  Two doses factor concentrate and gelatin sponge application were generally enough to prevent bleeding after circumcision of severe hemophilia A. Circumcision and low-dose FVIII protocol were not an additional risk for development of high-titer inhibitor.
authors.affiliation: Hemophilia and Thrombosis Center, Children's Hospital, Ain Shams University, Cairo, Egypt. elalfym@hotmail.com
authors.forename: Mohsen S
authors.initials: MS
authors.lastname: Elalfy
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Elbarbary
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Eldebeiky
authors.forename: Azza S
authors.initials: AS
authors.lastname: El Danasoury
mesh_terms: D000367:Age Factors; D019774:Blood Coagulation Factor Inhibitors; D002648:Child; D002675:Child, Preschool; D002944:Circumcision, Male / Q000009:adverse effects*; D005169:Factor VIII / Q000008:administration & dosage*; D005500:Follow-Up Studies; D005781:Gelatin Sponge, Absorbable / Q000008:administration & dosage*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy; D006470:Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D006490:Hemostatics; C078147:F8 protein, human; D005169:Factor VIII