Original Paper Acta Haematol 1999;102:42–46 Factor VIII Inhibitors in Patients with Hemophilia A Hale Ören Is ¸ ın Yaprak Gülersu I ˙ rken Departments of Pediatric Hematology, Dokuz Eylül University, Faculty of Medicine, and SSK Tepecik Hospital, Izmir, Turkey Received: August 21, 1998 Accepted: March 22, 1999 Dr. Hale Ören Dokuz Eylül University, Faculty of Medicine Department of Pediatric Hematology TR–35340 Balçova, I ˙ zmir (Turkey) Tel. +90 232 277 7777/4826, +90 232 259 9723 ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 1999 S. Karger AG, Basel 0001–5792/99/1021–0042$17.50/0 Accessible online at: http://BioMedNet.com/karger Key Words Factor VIII W Hemophilia A W Inhibitors Abstract In 58 hemophilia A patients aged 1–18 years (mean 9.5 B 4.7 years), the prevalence of inhibitors was found to be 27% by the Bethesda method in November 1995. Inhibi- tor activity was not detected in any of 14 patients with mild hemophilia while it was present in 9 of 27 (33%) patients with moderate, and 7 of 17 (41%) with severe disease. During follow-up, the inhibitors were transient in 10 of 16 patients (17%) and the prevalence of inhibi- tors was 10% at the end of the study. Our study has dem- onstrated that the patients’ age, factor VIII (F VIII) coagu- lant activity levels, type of F VIII replacement therapy, and frequency of F VIII administration affect inhibitor development, and these factors should be considered in the follow-up of hemophiliacs. Introduction One of the most serious problems in the treatment of patients with hemophilia A is the development of inhibi- tors of factor (F) VIII [1–3]. F VIII inhibitors are anti- bodies that develop in patients with hemophilia A in response to F VIII contained in various blood products, mostly neutralizing F VIII coagulant activity [2]. Since F VIII inhibitors make treatment of bleeding episodes much more difficult, it is important to evaluate patients’ inhibitor levels. Some of the factors thought to affect inhibitor development include the severity of the hemo- philia, the type and duration of clotting factor therapy, age and genetics of the patients [3, 4]. Development of inhibitors of F VIII occurs in about 5–10% of all patients with hemophilia A, but in 10–26% of severely affected individuals [4–8]. Treatment status of the patients affects inhibitor induction; since their immune systems have not yet been exposed to clotting factor thera- py, previously untreated patients show a higher rate of in- hibitor development than previously treated patients [9]. Also type of F VIII replacement therapy affects inhibitor formation [10]. In recent prospective studies the frequency of inhibitors in severe hemophilia A has varied from 28 to 52% in patients using intermediate-purity concentrates [11, 12]. In studies using recombinant F VIII concentrates, inhibitors formed in 19–24% of previously untransfused patients with severe hemophilia [6, 7, 13], and in studies using monoclonally purified plasma-derived concentrates, inhibitors developed in 6–18% [14, 15]. It has been shown that one third of the inhibitors will develop by age 4 years and more than 50% will develop by age 9 years [16, 17].