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. PATIENTS AND 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. CONCLUSION: 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.